BACKGROUND & AIMS: PURPOSE OF REVIEW:Given that the life expectancy and the burden of hypertension are projected to increase over the next decade, hypertensive heart disease (HHD) may be expected to play an even more central role in the pathophysiology of cardiovascular disease (CVD). A broader understanding of the features and underlying mechanisms that constitute HHD therefore is of paramount importance. RECENT FINDINGS:HHD is a condition that arises as a result of elevated blood pressure and constitutes a key underlying mechanism for cardiovascular morbidity and mortality. Historically, studies investigating HHD have primarily focused on left ventricular (LV) hypertrophy (LVH), but it is increasingly apparent that HHD encompasses a range of target-organ damage beyond LVH, including other cardiovascular structural and functional adaptations that may occur separately or concomitantly. HHD is characterized by micro- and macroscopic myocardial alterations, structural phenotypic adaptations, and functional changes that include cardiac fibrosis, and the remodeling of the atria and ventricles and the arterial system. In this review, we summarize the structural and functional alterations in the cardiac and vascular system that constitute HHD and underscore their underlying pathophysiology.

背景与目标： 审查目的：鉴于预期寿命和高血压负担将在未来十年内增加，因此，高血压心脏病（HHD）有望在心血管疾病（CVD）的病理生理学中发挥更加重要的作用。因此，对构成HHD的特征和基本机制的更广泛的理解至关重要。
最近的发现：HHD是由于血压升高而引起的疾病，并构成心血管疾病发病率和死亡率的关键潜在机制。从历史上看，研究HHD的研究主要集中在左心室肥大（LVH），但是越来越明显的是，HHD涵盖了LVH以外的一系列靶器官损害，包括可能单独或同时发生的其他心血管结构和功能适应性改变。 HHD的特征是微观和宏观的心肌改变，结构表型适应以及包括心脏纤维化，心房和心室以及动脉系统重塑在内的功能改变。在这篇综述中，我们总结了构成HHD的心脏和血管系统的结构和功能改变，并强调了其潜在的病理生理学。

BACKGROUND & AIMS: OBJECTIVE:In this review, we critically evaluate studies directly comparing the effects of plyometric vs. resistance training on skeletal muscle hypertrophy. METHODS:We conducted electronic searches of PubMed/MEDLINE, Scopus, SPORTDiscus, and Web of Science to find studies that explored the effects of plyometric vs. resistance training on muscle hypertrophy. RESULTS:Eight relevant studies were included in the review. Six studies compared the effects of plyometric vs. resistance training on muscle hypertrophy, while 2 studies explored the effects of combining plyometric and resistance training vs. isolated resistance training on acute anabolic signaling or muscle hypertrophy. Based on the results of these studies, we conclude that plyometric and resistance training may produce similar effects on whole muscle hypertrophy for the muscle groups of the lower extremities. Therefore, it seems that plyometric training has a greater potential for inducing increases in muscle size than previously thought. Despite the findings observed at the whole muscle level, the evidence for the effects of plyometric training on hypertrophy on the muscle fiber level is currently limited for drawing inferences. Compared to isolated resistance training, combining plyometric and resistance exercise does not seem to produce additive effects on anabolic signaling or muscle growth; however, this area requires future study. The limitations of the current body of evidence are that the findings are specific to (a) musculature of the lower extremities, (b) short-term training interventions that lasted up to 12 weeks, and (c) previously untrained or recreationally active participants. CONCLUSION:This review highlights that plyometric and resistance training interventions may produce similar effects on whole muscle hypertrophy, at least for the muscle groups of the lower extremities, in untrained and recreationally trained individuals, and over short-term (i.e., ≤12 weeks) intervention periods.

背景与目标： 目的：在这篇综述中，我们严格地评估了研究，直接比较了腹肌训练与阻力训练对骨骼肌肥大的影响。
方法：我们对PubMed / MEDLINE，Scopus，SPORTDiscus和Web of Science进行了电子搜索，以找到探索测厚与阻力训练对肌肉肥大的影响的研究。
结果：八项相关研究被纳入该评价。六项研究比较了体能测量和阻力训练对肌肉肥大的影响，而两项研究探讨了综合体能训练和阻力训练与孤立抵抗训练相结合对急性合成代谢信号或肌肉肥大的影响。根据这些研究的结果，我们得出结论，进行体力训练和阻力训练可能会对下肢的肌肉群的全肌肉肥大产生相似的影响。因此，似乎比以前认为的，体能训练具有更大的潜力来引起肌肉尺寸的增加。尽管在整个肌肉水平上都观察到了发现，但目前进行推论训练对肥大对肌肉纤维水平的影响的证据仍然有限。与孤立的阻力训练相比，将体能测验和阻力训练相结合似乎不会对合成代谢信号或肌肉生长产生累加作用。但是，这个领域需要进一步研究。当前证据的局限性在于，这些发现特定于（a）下肢的肌肉组织，（b）持续长达12周的短期训练干预措施，以及（c）以前未经训练或积极参加运动的参与者。
结论：这篇综述强调了，体力训练和阻力训练干预可能会对全肌肉肥大产生类似的影响，至少对于下肢的肌肉群，未经训练和接受过娱乐训练的个体以及短期（即≤12周）都可能产生类似的影响干预期。

BACKGROUND & AIMS: :Right ventricular (RV) pressure overload causes right ventricular hypertrophy in several types of pulmonary and congenital heart diseases. The associated cardiac dysfunction has generally been attributed to alterations in RV function. However, due to global neurohormonal adaptations and mechanical ventricular interaction left ventricular (LV) function could be affected as well.Therefore,LV function, RV function and their interaction were studied in rats with monocrotaline (MCT)-induced RV hypertrophy and control rats. MCT (30 mg/kg) was used to induce pulmonary hypertension, which resulted, after 28 days, in marked RV hypertrophy (RV-weight: control 220 +/- 15,MCT 437 +/- 34mg,p < 0.05). In Langendorff-perfused hearts with balloons inserted in both the LV and the RV, the diastolic pressure-volume relations showed increased stiffness, and relaxation was prolonged in the LV and RV in the MCT group compared to controls. In the MCT group, developed pressures were increased only in the RV. An increase of LV volume increased RV diastolic pressure to a similar extent in both groups. However, an increase in RV volume did not affect LV diastolic pressure in controls, but significantly increased LV diastolic pressure in the MCT group. LV and RV developed pressure-volume relations were not affected. Calculated circumferential end-diastolic wall stresses (sigma) were larger in the MCT group (LV-sigma: 0.55 +/- 0.02, RV-sigma: 1.94 +/- 0.30 kN/m(2), both p< 0.05 to control) compared to controls (LV-sigma: 0.34 +/- 0.06,RV-sigma: 1.23 +/- 0.46 kN/m2). In the MCT group, collagen content was increased in the LV, septum and RV compared to controls. In conclusion, structural changes of the RV and LV result in depressed LV diastolic function during RV hypertrophy.

背景与目标： ：右心室（RV）压力超负荷会导致多种肺和先天性心脏病的右心室肥大。相关的心脏功能障碍通常归因于RV功能的改变。然而，由于整体的神经激素适应和机械性的心室相互作用，左心室（LV）功能也可能受到影响。因此，在MCA诱发的RV中，左室功能，RV功能及其相互作用受到了研究。 MCT（30 mg / kg）用于诱发肺动脉高压，在28天后导致明显的RV肥大（RV重量：对照组220 / -15，MCT 437 /-34mg，p <0.05）。与对照相比，在MCT组中，在LV和RV均插入有气球的Langendorff灌注心脏中，舒张压-容积关系显示出增加的刚度，并且LV和RV的舒张时间延长。在MCT组中，仅RV出现的压力增加。两组左室容积的增加使右室舒张压增加到相似的程度。但是，RV体积的增加并未影响对照组的左室舒​​张压，但在MCT组中却显着增加了左室舒张压。左室和右室发展的压力-体积关系不受影响。与MCT组相比，计算得出的舒张末期壁舒张末期壁应力（sigma）更大（LV-sigma：0.55 /-0.02，RV-sigma：1.94 /-0.30 kN / m（2），与对照相比均p <0.05）控件（LV-sigma：0.34 /-0.06，RV-sigma：1.23 /-0.46 kN / m2）。在MCT组中，与对照组相比，LV，隔膜和RV中的胶原蛋白含量增加。总之，RV和LV的结构变化会导致RV肥大期间LV舒张功能降低。

BACKGROUND & AIMS: :Hypertrophy in capillary malformation (CM) may be present at birth or manifest itself later in life. To gain insight into the pathology of hypertrophic CM, we investigated a series of 11 excisional biopsies of hypertrophic lips.All biopsies showed dilated thin-walled microvessels in the superficial dermis without a neural component. However, large multinodular conglomerates of thick-walled vessels with a substantial increase in nerve fibers were found in the deeper parts of the lesions. These veins extended deep into the facial musculature. Hypertrophy in CM is caused by venous malformation underlying the CM. So CM associated with hypertrophy should be considered as Capillary Venous malformations.

背景与目标： ：毛细血管畸形（CM）的肥大可能在出生时就出现，或者在以后的生活中表现出来。为了深入了解肥厚性CM的病理，我们对11例肥厚性双唇切除活检进行了一系列研究。所有活检均显示浅层真皮中的扩张性薄壁微血管无神经成分。但是，在病变的较深部分发现了厚壁血管的大型多结节性结块，其中神经纤维显着增加。这些静脉深入面部肌肉组织。 CM肥大是由CM下方的静脉畸形引起的。因此，与肥大相关的CM应被认为是毛细血管静脉畸形。

BACKGROUND & AIMS: AIM:To address to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. METHODS:The ability of the liver to regenerate is remarkable on both clinical and biological grounds. Basic mechanisms underlying this process have been intensively investigated. However, it is still debated to what extent hypertrophy and hyperplasia contribute to liver mass restoration after major tissue loss. We addressed this issue using a genetically tagged system. We were able to follow the fate of single transplanted hepatocytes during the regenerative response elicited by 2/3 partial surgical hepatectomy (PH) in rats. Clusters of transplanted cells were 3D reconstructed and their size distribution was evaluated over time after PH. RESULTS:Liver size and liver DNA content were largely recovered 10 d post-PH, as expected (e.g., total DNA/liver/100 g b.w. was 6.37 ± 0.21 before PH and returned to 6.10 ± 0.36 10 d after PH). Data indicated that about 2/3 of the original residual hepatocytes entered S-phase in response to PH. Analysis of cluster size distribution at 24, 48, 96 h and 10 d after PH revealed that about half of the remnant hepatocytes completed at least 2 cell cycles. Average size of hepatocytes increased at 24 h (248.50 μm2 ± 7.82 μm2, P = 0.0015), but returned to control values throughout the regenerative process (up to 10 d post-PH, 197.9 μm2 ± 6.44 μm2, P = 0.11). A sizeable fraction of the remnant hepatocyte population does not participate actively in tissue mass restoration. CONCLUSION:Hyperplasia stands as the major mechanism contributing to liver mass restoration after PH, with hypertrophy playing a transient role in the process.

背景与目标： 目的：探讨肥大和增生在主要组织丢失后在多大程度上有助于肝脏肿块的恢复。
方法：无论从临床还是生物学的角度来看，肝脏的再生能力都很显着。深入研究了此过程的基本机制。然而，仍存在争议，在主要组织丢失后，肥大和增生在多大程度上有助于肝块的恢复。我们使用基因标记的系统解决了这个问题。在2/3部分外科手术肝切除术（PH）引起的再生反应过程中，我们能够追踪单个移植肝细胞的命运。 PH移植后，将移植的细胞簇进行3D重建，并评估其大小分布。
结果：在PH后10 d，肝脏大小和肝脏DNA含量在很大程度上恢复了（如在PH前的总DNA /肝脏/ 100 g b.w.为6.37±0.21，而在PH后10 d恢复至6.10±0.36）。数据表明，约有2/3的原始残余肝细胞响应PH而进入S期。 PH后24、48、96 h和10 d的簇大小分布分析表明，大约一半的残留肝细胞完成了至少2个细胞周期。肝细胞的平均大小在24 h时增加（248.50μm2±7.82μm2，P = 0.0015），但在整个再生过程中恢复到对照值（PH后长达10 d，197.9μm2±6.44μm2，P = 0.11）。相当一部分肝细胞残余不能积极参与组织块的恢复。
结论：增生是造成PH后肝脏肿块恢复的主要机制，肥大在此过程中起暂时作用。

BACKGROUND & AIMS: Background & objectives:Inferior turbinate hypertrophy (ITH) is a common condition causing nasal obstruction. This study was undertaken to compare the efficacy of potassium titanyl phosphate (KTP) laser and diode laser in the reduction of the turbinate size. Methods:This randomized controlled trial included 209 patients with ITH. Pre-operative symptoms were assessed based on the Nasal Obstruction Symptom Evaluation (NOSE) score. Diagnostic nasal endoscopy was done to rule out other nasal sinuses. Nasal mucociliary clearance was measured by saccharin transit time (STT). Postoperatively, the NOSE score, STT and complications were assessed at days one and two, at one week, one month and three months. Results:Of the 209 patients analyzed at day one, the median NOSE score was 50 in the diode group and 40 in the KTP group, and at three months, 15 in the diode group and five in the KTP group. KTP laser showed a 93 per cent improvement in the NOSE score as compared to 77 per cent improvement shown by diode laser group. Among the intra-operative complications, of the 104 patients in the diode group, 6.73 per cent had burning sensation and 91.43 per cent had bleeding, and of 105 patients in the KTP group, 54.29 per cent had burning sensation and 36.54 per cent had bleeding. Among the post-operative complications in the KTP group, 32 and 34 per cent had bloody nasal discharge on days one and two, compared to 12 and 14 per cent in diode group. Crusting was present in 61 and 49 per cent on days one and two in KTP group as compared to 9 and 15 per cent in diode group, respectively. In the KTP group 30 per cent had synechiae as compared to 10 per cent in diode group. Interpretation & conclusions:KTP laser was more efficacious than diode laser in improving the NOSE scores but with slightly increased rate of complications in early post-operative period. Both the lasers impaired the mucociliary clearance mechanism of the nose till three months of post-operative follow up.

背景与目标： 背景与目的：下鼻甲肥大（ITH）是导致鼻塞的常见病。进行这项研究以比较磷酸钛氧钾（KTP）激光和二极管激光在减小鼻甲大小方面的功效。
方法：该随机对照试验包括209例ITH患者。根据鼻塞症状评估（NOSE）评分评估术前症状。进行了诊断性鼻内窥镜检查以排除其他鼻窦。鼻粘膜纤毛清除率通过糖精转运时间（STT）测量。术后第1天和第2天，第1周，第1个月和第3个月评估NOSE评分，STT和并发症。
结果：在第一天分析的209例患者中，二极管组的NOSE中位数为50，KTP组为40，三个月时，二极管组为15，KTP组为5。 KTP激光器的NOSE得分提高了93％，而二极管激光器组则提高了77％。在术中并发症中，二极体组104例患者中，烧灼感为6.73％，出血为91.43％，KTP组的105例患者中，烧灼感为54.29％，出血为36.54％ 。在KTP组的术后并发症中，分别在第一天和第二天有32％和34％的人流鼻血，而二极管组则分别为12％和14％。 KTP组第1天和第2天的结壳率分别为61％和49％，而二极管组的结壳率分别为9％和15％。在KTP组中，有30％的人患有粘连症，而在二极管组中则为10％。
解释与结论：KTP激光在改善NOSE评分方面比二极管激光更有效，但术后早期的并发症发生率略有增加。两种激光都削弱了鼻子的粘膜纤毛清除机制，直到术后三个月随访为止。

BACKGROUND & AIMS: :Transition from compensated to decompensated left ventricular hypertrophy (LVH) is accompanied by functional and structural changes. Here, the aim was to evaluate dystrophin expression in murine models and human subjects with LVH by transverse aortic constriction (TAC) and aortic stenosis (AS), respectively. We determined whether doxycycline (Doxy) prevented dystrophin expression and myocardial stiffness in mice. Additionally, ventricular function recovery was evaluated in patients 1 year after surgery. Mice were subjected to TAC and monitored for 3 weeks. A second group received Doxy treatment after TAC. Patients with AS were stratified by normal left ventricular end-diastolic wall stress (LVEDWS) and high LVEDWS, and groups were compared. In mice, LVH decreased inotropism and increased myocardial stiffness associated with a dystrophin breakdown and a decreased mitochondrial O2 uptake (MitoMVO2). These alterations were attenuated by Doxy. Patients with high LVEDWS showed similar results to those observed in mice. A correlation between dystrophin and myocardial stiffness was observed in both mice and humans. Systolic function at 1 year post-surgery was only recovered in the normal-LVEDWS group. In summary, mice and humans present diastolic dysfunction associated with dystrophin degradation. The recovery of ventricular function was observed only in patients with normal LVEDWS and without dystrophin degradation. In mice, Doxy improved MitoMVO2. Based on our results it is concluded that the LVH with high LVEDWS is associated to a degradation of dystrophin and increase of myocardial stiffness. At least in a murine model these alterations were attenuated after the administration of a matrix metalloprotease inhibitor.

背景与目标： 从代偿性向代偿性失衡的左心室肥大（LVH）的转变伴随着功能和结构的变化。在这里，目的是通过横向主动脉缩窄（TAC）和主动脉狭窄（AS）评估鼠模型和LVH人体受试者中的肌营养不良蛋白表达。我们确定强力霉素（Doxy）是否能预防小鼠中的肌营养不良蛋白表达和心肌僵硬。此外，术后1年评估患者的心室功能恢复。对小鼠进行TAC并监测3周。第二组在TAC后接受Doxy治疗。 AS患者按正常左心室舒张末期壁应力（LVEDWS）和高LVEDWS进行分层，并比较各组。在小鼠中，LVH降低了肌力，并增加了肌营养不良蛋白的分解和线粒体O2摄取（MitoMVO2）的减少，从而增加了心肌的硬度。这些改变被Doxy减弱了。 LVEDWS高的患者显示的结果与小鼠观察到的结果相似。在小鼠和人类中都观察到肌营养不良蛋白与心肌硬度之间的相关性。术后1年的收缩功能仅在正常LVEDWS组中得以恢复。总之，小鼠和人类表现出与肌营养不良蛋白降解相关的舒张功能障碍。仅在LVEDWS正常且无肌营养不良蛋白降解的患者中观察到心室功能的恢复。在小鼠中，Doxy改善了MitoMVO2。根据我们的结果，可以得出结论，LVEDWS高的LVH与肌营养不良蛋白的降解和心肌硬度的增加有关。至少在鼠模型中，在施用基质金属蛋白酶抑制剂后，这些改变被减弱了。

BACKGROUND & AIMS: :Increasing evidence suggests that a mismatch between angiogenesis and myocardial growth contributes to the transition from adaptive cardiac hypertrophy to heart failure following pressure overload. Syndecan-4 is a transmembrane proteoglycan that binds to growth factors and extracellular matrix proteins and is critical in focal adhesion formation. However, its effects on coronary angiogenesis during pressure overload-induced heart failure have not been studied. Here, we hypothesize that syndecan-4 modulates cardiac remodeling in response to pressure overload through its ability to regulate adaptive angiogenesis. Syndecan-4 knockout (syndecan-4 KO) and wild-type (WT) mice were subjected to pressure overload induced by transverse aortic constriction (TAC). Syndecan-4 KO mice exhibited reduced capillary density, attenuated cardiomyocyte size, and worsened left ventricular cardiac function after TAC surgery compared with WT mice. Moreover, syndecan-4 KO mice showed a significant decrease in protein kinase C alpha expression. Our data suggest that syndecan-4 is essential for the compensated hypertrophy and the maintenance of cardiac function during the process of heart failure following pressure overload.

背景与目标： ：越来越多的证据表明，在压力超负荷后，血管新生与心肌生长之间的不匹配会导致从适应性心脏肥大向心力衰竭的转变。 Syndecan-4是一种跨膜蛋白聚糖，可与生长因子和细胞外基质蛋白结合，对形成粘着斑至关重要。然而，尚未研究其在压力超负荷引起的心力衰竭期间对冠状血管生成的影响。在这里，我们假设syndecan-4通过调节适应性血管新生的能力来调节心脏重塑，以应对压力超负荷。 Syndecan-4基因敲除（syndecan-4 KO）和野生型（WT）小鼠受到横动脉主动脉缩窄（TAC）诱导的压力超负荷。与WT小鼠相比，在TAC手术后，Syndecan-4 KO小鼠的毛细血管密度降低，心肌细胞大小减少和左心室心脏功能恶化。此外，syndecan-4 KO小鼠显示蛋白激酶Cα表达明显降低。我们的数据表明，在压力超负荷后心力衰竭过程中，syndecan-4对于代偿性肥大和维持心功能至关重要。

BACKGROUND & AIMS: BACKGROUND AND AIM:Secreted frizzled-related protein 2 (sFRP2) has been reported to be involved in cardiovascular diseases. However, its role in cardiac hypertrophy induced by pressure overload is still elusive. We aimed to examine the role of sFRP2 in the development of cardiac hypertrophy in vivo and in vitro. METHODS AND RESULTS:Following cardiac hypertrophy stimulated by aortic banding (AB), the expression of sFRP2 was downregulated in the hypertrophic ventricle. Adeno-associated virus 9 (AAV9) was injected through the tail vein to overexpress sFRP2 in the mouse myocardium. Overexpression of sFRP2 alleviated cardiomyocyte hypertrophy and interstitial fibrosis, as identified by the reduced cardiomyocyte cross-sectional area, heart weight/body weight ratio, and left ventricular (LV) collagen ratio. Additionally, sFRP2 decreased cardiomyocyte apoptosis induced by pressure overload. Western blot showed that sFRP2 prevented the expression of active β-catenin. The Wnt/β-catenin agonist LiCl (1 mmol/kg) abolished the inhibitory effects of sFRP2 on cardiac hypertrophy and apoptosis, as evidenced by the increased cross-sectional area and LV collagen ratio and the deterioration of echocardiographic data. CONCLUSION:Our study indicated that decreased sFRP2 levels were observed in failing mouse hearts. Overexpression of sFRP2 attenuated myocyte hypertrophy and interstitial fibrosis induced by hypertrophic stimuli by inhibiting the Wnt/β-catenin pathway. We revealed that sFRP2 may be a promising therapeutic target for the development of cardiac remodeling.

背景与目标： 背景与目的：据报道，卷曲的相关蛋白2（sFRP2）与心血管疾病有关。然而，它在由压力超负荷引起的心脏肥大中的作用仍然难以捉摸。我们旨在研究sFRP2在体内和体外心脏肥大发展中的作用。
方法和结果：在主动脉束带（AB）刺激的心肌肥大之后，sFRP2的表达在肥厚性心室中被下调。通过尾静脉注射腺相关病毒9（AAV9）以在小鼠心肌中过表达sFRP2。 sFRP2的过表达减轻了心肌肥大和间质纤维化，这通过减少的心肌细胞横截面积，心脏重量/体重比和左心室（LV）胶原蛋白比来确定。另外，sFRP2减少了压力超负荷引起的心肌细胞凋亡。 Western印迹表明，sFRP2阻止了活性β-catenin的表达。 Wnt /β-catenin激动剂LiCl（1 mmol / kg）取消了sFRP2对心脏肥大和细胞凋亡的抑制作用，这一点由横截面积和LV胶原比例的增加以及超声心动图数据的恶化所证明。
结论：我们的研究表明在衰竭的小鼠心脏中观察到sFRP2水平降低。 sFRP2的过表达通过抑制Wnt /β-catenin途径减弱了肥厚性刺激诱导的心肌肥大和间质纤维化。我们发现，sFRP2可能是心脏重塑发展的有希望的治疗靶标。

BACKGROUND & AIMS: OBJECTIVE:In patients with type 2 diabetes, left ventricular hypertrophy (LVH) predicts cardiovascular events, and the prevention of LVH is cardioprotective. We sought to compare the effect of ACE versus non-ACE inhibitor therapy on incident electrocardiographic (ECG) evidence of LVH (ECG-LVH). RESEARCH DESIGN AND METHODS:This prespecified study compared the incidence of ECG-LVH by Sokolow-Lyon and Cornell voltage criteria in 816 hypertensive type 2 diabetic patients of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT), who had no ECG-LVH at baseline and were randomly assigned to at least 3 years of blinded ACE inhibition with trandolapril (2 mg/day) or to non-ACE inhibitor therapy. Treatment was titrated to systolic/diastolic blood pressure <130/80 mmHg. ECG readings were centralized and blinded to treatment. RESULTS:Baseline characteristics of the two groups were similar. Over a median (interquartile range) follow-up of 36 (24-48) months, 13 of the 423 patients (3.1%) receiving trandolapril compared with 31 of the 376 patients (8.2%) receiving non-ACE inhibitor therapy developed ECG-LVH (hazard ratio [HR] 0.34 [95% CI 0.18-0.65], P = 0.0012 unadjusted, and 0.35 [0.18-0.68], P = 0.0018 adjusted for predefined baseline covariates). The HR was significant even after adjustment for follow-up blood pressure and blood pressure reduction versus baseline. Compared with baseline, both Sokolow-Lyon and Cornell voltages significantly decreased with trandolapril but did not change with non-ACE inhibitor therapy. CONCLUSIONS:ACE inhibition has a specific protective effect against the development of ECG-LVH that is additional to its blood pressure-lowering effect. Because ECG-LVH is a strong cardiovascular risk factor in people with hypertension and diabetes, early ACE inhibition may be cardioprotective in this population.

背景与目标： 目的：在2型糖尿病患者中，左心室肥大（LVH）可以预测心血管事件，对LVH的预防具有心脏保护作用。我们试图比较ACE与非ACE抑制剂治疗对LVH的入射心电图（ECG）证据（ECG-LVH）的影响。
研究设计和方法：这项预先设定的研究比较了816例Bergamo肾病糖尿病并发症试验（BENEDICT）的高血压2型糖尿病患者的Sokolow-Lyon和Cornell电压标准对ECG-LVH的发生率，他们在基线和基线时均没有ECG-LVH随机分配至少3年使用trandolapril（2 mg /天）的ACE盲治疗或非ACE抑制剂治疗。将治疗滴定至收缩压/舒张压<130/80 mmHg。心电图读数集中并且对治疗不知情。
结果：两组的基线特征相似。在36（24-48）个月的中位（四分位间距）随访中，接受trandolapril治疗的423例患者中有13例（3.1％）接受了非ACE抑制剂治疗的376例患者（8.2％）中的31例发展了ECG- LVH（危险比[HR] 0.34 [95％CI 0.18-0.65]，未调整P = 0.0012，0.35 [0.18-0.68]，对于预定义的基线协变量已调整P = 0.0018）。即使在调整了后续血压和相对于基线的血压降低后，HR仍显着。与基线相比，使用trandolapril的Sokolow-Lyon和Cornell电压均显着降低，但使用非ACE抑制剂治疗则无变化。
结论：ACE抑制对ECG-LVH的发展具有特定的保护作用，这是其降低血压的作用。由于ECG-LVH在高血压和糖尿病患者中是很强的心血管危险因素，因此早期ACE抑制可能对该人群具有心脏保护作用。

BACKGROUND & AIMS: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity in hypertensive patients. The effects of diuretics on LVH have raised controversies, but recent studies suggest that diuretics are able to reduce LVH in hypertensive patients, mainly through a reduction in ventricular diameter. The present multicenter open study was designed to test the effects of indapamide, a widely used nonthiazide diuretic, on LVH in patients with essential hypertension. Patients had to have mild-to-moderate essential hypertension (supine diastolic blood pressure [sDBP] 95 to 115 mm Hg) with echocardiographic evidence of LVH (left ventricular mass index [LVMI] > 130 g/m2 for men and > 110 g/m2 for women). After a 2 week placebo run-in period, eligible patients underwent a 6 month treatment with 2.5 mg indapamide daily. All echograms were performed by the same investigator before and after 6 months of indapamide. Clinical and biological acceptability and quality of life (visual analog scale) were also studied. One hundred and thirty patients were included in the study and 112 completed the trial. Indapamide induced a significant reduction i systolic and diastolic blood pressures. Indapamide induced a marked reduction in posterior wall thickness (from 12.1 +/- 2.0 to 11.2 +/- 1.6 mm) and in interventricular wall thickness (from 12.7 +/- 1.7 to 11.8 +/- 1.9 mm; each P < .001) and a slight decrease in left ventricular diameter (P = .049). This resulted in a 13% reduction in LVMI (from 161.9 +/- 37.9 to 140.7 +/- 33.8 g/m2, P < .001). Left ventricular fractional shortening remained unchanged. There was no significant relation between changes in LVMI and changes in systolic, diastolic, or mean blood pressure. No significant adverse clinical or biological effects were reported during the study. The increased score of the visual analog scale indicated that overall well-being was improved (P < .001). Our study indicates that indapamide, in addition to blood pressure control, is able to reduce LVH. This effect was achieved mainly through a reduction in wall thicknesses rather than in internal cavity diameter.

背景与目标： 左心室肥大（LVH）是高血压患者心血管疾病的主要危险因素。利尿剂对LVH的影响引起了争议，但最近的研究表明，利尿剂能够降低高血压患者的LVH，主要是通过减小心室直径。当前的多中心开放研究旨在测试吲哚帕胺（一种广泛使用的非噻嗪类利尿剂）对原发性高血压患者左室肥厚的影响。患者必须患有轻度至中度的原发性高血压（仰卧舒张压[sDBP] 95至115 mm Hg），并伴有LVH的超声心动图证据（男性左心室质量指数[LVMI]> 130 g / m2，> 110 g / m2）平方米（女士）。经过2周的安慰剂磨合期后，合格的患者每天接受2.5毫克吲达帕胺治疗6个月。在吲达帕胺治疗6个月之前和之后，所有超声检查均由同一位研究人员进行。还研究了临床和生物学可接受性以及生活质量（视觉模拟量表）。这项研究纳入了130位患者，其中112位完成了试验。吲达帕胺引起收缩压和舒张压的显着降低。吲达帕胺引起后壁厚度（从12.1 /-2.0降低到11.2 /-1.6 mm）和心室壁厚度（从12.7 /-1.7降低到11.8 /-1.9 mm;每个P <.001）显着降低，并略有降低在左心室直径（P = .049）。这导致LVMI降低了13％（从161.9 /-37.9降至140.7 /-33.8 g / m2，P <.001）。左心室分数缩短保持不变。 LVMI的变化与收缩压，舒张压或平均血压的变化之间没有显着关系。在研究过程中，未见明显的不良临床或生物学影响。视觉模拟量表评分的增加表明总体健康水平得到了改善（P <.001）。我们的研究表明，吲达帕胺除了可以控制血压外，还可以降低LVH。这种效果主要是通过减小壁厚而不是减小内腔直径来实现的。

BACKGROUND & AIMS: :This study investigated the role of renal nitric oxide synthase (NOS), endothelin, and possible mechanisms of renovascular dysfunction in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were treated for 8 wk with high salt diet (4% NaCl) alone or in combination with the ET(A) receptor antagonist LU135252 (60 mg/kg per d). Salt loading markedly increased NOS activity (pmol citrulline/mg protein per min) in renal cortex and medulla in DR but not in DS rats by 270 and 246%, respectively. Hypertension in DS rats was associated with renal artery hypertrophy, increased vascular and renal endothelin-1 (ET-1) protein content, and glomerulosclerosis. In the renal artery but not in the aorta of hypertensive DS rats, endothelium-dependent relaxation to acetylcholine was unchanged; however, endothelial dysfunction due to enhanced prostanoid-mediated, endothelium-dependent contractions and attenuation of basal nitric oxide release was present. Treatment with LU135252 reduced hypertension in part, but completely prevented activation of tissue ET-1 without affecting ET-3 levels. This was associated with a slight increase of renal NOS activity, normalization of endothelial dysfunction and renal artery hypertrophy, and marked attenuation of glomerulosclerosis. Thus, DS rats fail to increase NOS activity in response to salt loading. This abnormality may predispose to activation of the tissue ET-1 system, abnormal renal vasoconstriction, and renal injury. Chronic ET(A) receptor blockade normalized salt-induced changes in the renal artery and reduced glomerular injury, suggesting therapeutic potential for ET antagonists in salt-sensitive forms of hypertension.

背景与目标： ：本研究调查了盐敏感型高血压中肾一氧化氮合酶（NOS），内皮素的作用以及肾血管功能障碍的可能机制。盐敏感性（DS）和抗盐（DR）的Dahl大鼠单独或与ET（A）受体拮抗剂LU135252（60 mg / kg / d）高盐饮食（4％NaCl）一起治疗8周。盐负荷显着增加了DR大鼠的肾皮质和髓质中的NOS活性（pmol瓜氨酸/ mg蛋白/分钟），而DS大鼠中的NOS活性则没有分别增加270和246％。 DS大鼠的高血压与肾动脉肥大，血管和肾脏内皮素1（ET-1）蛋白含量增加以及肾小球硬化有关。在高血压DS大鼠的肾动脉而非主动脉中，对乙酰胆碱的内皮依赖性舒张作用没有改变。然而，由于前列腺素介导的内皮依赖性收缩增强和基底一氧化氮释放减弱而引起的内皮功能障碍。 LU135252的治疗可以部分减轻高血压，但完全可以阻止ET-1组织的活化，而不会影响ET-3的水平。这与肾NOS活性略有增加，内皮功能障碍和肾动脉肥大正常化以及肾小球硬化明显减轻有关。因此，DS大鼠不能响应盐负荷而增加NOS活性。这种异常可能导致组织ET-1系统激活，异常的肾血管收缩和肾脏损伤。慢性ET（A）受体阻滞了盐引起的肾动脉变化的正常化，并减少了肾小球损伤，这表明ET拮抗剂在盐敏感性形式的高血压中具有治疗潜力。

BACKGROUND & AIMS: BACKGROUND:Endothelial nitric oxide synthase produces nitric oxide which is involved in many physiologic regulatory functions. Variable number of tandem repeats in intron 4 of endothelial nitric oxide synthase gene are reported to be associated with blood pressure regulation. Nitric oxide is involved in regulation of cardiomyocyte genes but it is not known If endothelial nitric oxide synthase 4 gene polymorphisms are related with left ventricular hypertrophy. We studied endothelial nitric oxide synthase 4a/b allele status in hypertensive and normotensive patients and echocardiographic parameters in a subgroup of hypertensive group. METHODS:We performed a case-control study involving 110 Turkish hypertensive patients and 87 controls. All subjects were genotyped for endothelial nitric oxide synthase 4a/b polymorphism. Echocardiographic measurements were obtained in 94 of the hypertensive patients. RESULTS:Endothelial nitric oxide synthase 4a/b genotype frequencies were 6.4%, 23.6%, 70% in hypertensives and 1.1%, 18.4%, 80.5% in controls for a/a, a/b, b/b, respectively. Left ventricular dimensions, mass and diastolic indices were not different across endothelial nitric oxide synthase 4 genotypes. Patients with 4a/a genotype had higher interventricular septal thickness than the other group; 14.83(1.6), 11.91(1.51), 12.21(1.56) for a/a, a/b, b/b, respectively and p = 0.0001. CONCLUSION:Endothelial nitric oxide synthase 4a/b gene polymorphism is not associated with hypertension in Turkish patients. 4a/a genotype was associated with higher interventricular septal thickness in hypertensive patients.

背景与目标： 背景：内皮型一氧化氮合酶产生的一氧化氮参与许多生理调节功能。据报道，内皮一氧化氮合酶基因的内含子4中的串联重复数目可变，这与血压调节有关。一氧化氮参与心肌细胞基因的调控，但尚不清楚内皮型一氧化氮合酶4基因多态性是否与左心室肥大有关。我们研究了高血压和血压正常患者的内皮一氧化氮合酶4a / b等位基因状态以及高血压亚组的超声心动图参数。
方法：我们进行了一项病例对照研究，涉及110名土耳其高血压患者和87名对照。对所有受试者的内皮型一氧化氮合酶4a / b多态性进行基因分型。 94名高血压患者获得了超声心动图测量结果。
结果：高血压患者的内皮型一氧化氮合酶4a / b基因型频率分别为6.4％，23.6％，70％和a / a，a / b，b / b对照组的1.1％，18.4％，80.5％。内皮型一氧化氮合酶4基因型的左心室尺寸，质量和舒张指数没有差异。基因型为4a / a的患者的室间隔厚度比另一组高。 a / a，a / b，b / b分别为14.83（1.6），11.91（1.51），12.21（1.56），p = 0.0001。
结论：土耳其人内皮型一氧化氮合酶4a / b基因多态性与高血压无关。基因型4a / a与高血压患者较高的室间隔厚度有关。

BACKGROUND & AIMS: :Nicotinamide phosphoribosyltransferase (Nampt) is involved in the development of cardiac hypertrophy. Transient receptor potential canonical channel 1 (TRPC1) and endoplasmic reticulum stress (ER stress) are regarded as critical pathways in cardiac hypertrophy. Therefore, we hypothesizedthat TRPC1 might be associated with ER stress in Nampt-induced cardiac hypertrophy. CulturedH9c2cardiomyocyteswereexposed to Namptfor different timesand the expression of markers of cardiomyocyte hypertrophy and ER stress, as well as TRPC1 were detected. Moreover, specific TRPC1-shRNA (short hairpin RNA) expressing plasmid was transfected to knockdown TRPC1 expression before Nampt stimulation. Thapsigargin was used as an agonist and pravastatin was employed as an inhibitor of ER stress. The results demonstrated that exposure of H9c2 cells to 100 ng/mL Nampt for 24h, 48h or 72h significantly increased the expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), markers of ER stress and TRPC1. The Nampt-induced expression of TRPC1 was attenuated by pre-treatment with pravastatin, whereas promoted by pre-treatment with thapsigargin. Furthermore, transfection of TRPC1-shRNA for 48h partially inhibited Nampt-induced expression of ER stress markers and BNP in H9c2 cells. Our data suggest that TRPC1 might play an important role in cardiomyocyte hypertrophy induced by Namptinan ER stress-dependent way.

背景与目标： ：Nicotinamide磷酸核糖基转移酶（Nampt）与心脏肥大的发展有关。瞬时受体电位规范通道1（TRPC1）和内质网应激（ER应激）被认为是心肌肥大的关键途径。因此，我们假设TRPC1可能与Nampt诱发的心肌肥大中的ER应激有关。将培养的H9c2心肌细胞暴露于Nampt不同的时间，并检测心肌细胞肥大和内质网应激的标志物以及TRPC1的表达。而且，在Nampt刺激之前，将特异性表达TRPC1-shRNA（短发夹RNA）的表达质粒转染以降低TRPC1的表达。 Thapsigargin被用作激动剂，普伐他汀被用作ER应激的抑制剂。结果表明，H9c2细胞在100 ng / mL Nampt中暴露24h，48h或72h会显着增加心房利钠肽（ANP），脑利钠肽（BNP），ER应激和TRPC1的表达。普伐他汀预处理可减弱Nampt诱导的TRPC1表达，而thapsigargin预处理则可促进Nampt诱导的TRPC1表达。此外，将TRPC1-shRNA转染48h可部分抑制Nampt诱导的H9c2细胞中ER应激标志物和BNP的表达。我们的数据表明，TRPC1可能在Namptinan ER应激依赖性方式诱导的心肌肥大中起重要作用。

BACKGROUND & AIMS: :Identifying the key factor mediating pathological cardiac hypertrophy is critically important for developing the strategy to protect against heart failure. Bone morphogenetic protein-4 (BMP4) is a mechanosensitive and proinflammatory gene. In this study, we investigated the role of BMP4 in cardiac hypertrophy, apoptosis, and fibrosis in experimentally pathological cardiac hypertrophy. The in vivo pathological cardiac hypertrophy models were induced by pressure-overload and angiotensin (Ang) II constant infusion in mice, and the in vitro model was induced by Ang II exposure to cultured cardiomyocytes. The expression of BMP4 increased in pressure overload, Ang II constant infusion-induced pathological cardiac hypertrophy, but not in swimming exercise-induced physiological cardiac hypertrophy in mice. BMP4 expression also increased in Ang II-induced cardiomyocyte hypertrophy in vitro. In turn, BMP4 induced cardiomyocyte hypertrophy, apoptosis, and cardiac fibrosis, and these pathological consequences were inhibited by the treatment with BMP4 inhibitors noggin and DMH1. Moreover, Ang II-induced cardiomyocyte hypertrophy was inhibited by BMP4 inhibitors. The underlying mechanism that BMP4-induced cardiomyocyte hypertrophy and apoptosis was through increasing NADPH oxidase 4 expression and reactive oxygen species-dependent pathways. Lentivirus-mediated overexpression of BMP4 recapitulated hypertrophy and apoptosis in cultured cardiomyocytes. BMP4 inhibitor DMH1 inhibited pressure overload-induced cardiac hypertrophy in mice in vivo. The plasma BMP4 level of heart failure patients was increased compared with that of subjects without heart failure. In summary, we conclude that BMP4 is a mediator and novel therapeutic target for pathological cardiac hypertrophy.

背景与目标： ：确定介导病理性心脏肥大的关键因素对于制定预防心力衰竭的策略至关重要。骨形态发生蛋白4（BMP4）是机械敏感和促炎基因。在这项研究中，我们调查了BMP4在实验性病理性心肌肥大中在心肌肥大，细胞凋亡和纤维化中的作用。通过压力超负荷和血管紧张素（Ang）II恒定输注诱导小鼠体内病理性心肌肥大模型，并通过将Ang II暴露于培养的心肌细胞诱导体外模型。在压力超负荷，Ang II持续输注引起的病理性心肌肥大中，BMP4的表达增加，但在游泳运动引起的小鼠生理性心肌肥大中则没有。在体外，Ang II诱导的心肌肥大中BMP4表达也增加。反过来，BMP4诱导心肌肥大，凋亡和心脏纤维化，而这些病理后果被BMP4抑制剂头蛋白和DMH1的治疗所抑制。此外，Ang II诱导的心肌肥大被BMP4抑制剂抑制。 BMP4诱导心肌肥大和凋亡的潜在机制是通过增加NADPH氧化酶4的表达和活性氧依赖性途径。慢病毒介导的BMP4的过表达在培养的心肌细胞中概括了肥大和细胞凋亡。 BMP4抑制剂DMH1在体内抑制了压力超负荷引起的心脏肥大。与没有心力衰竭的受试者相比，心力衰竭患者的血浆BMP4水平升高。总之，我们得出结论，BMP4是病理性心脏肥大的介体和新的治疗靶标。