Induction of myocardial connective tissue growth factor in pacing-induced heart failure in pigs

AIMS: Connective tissue growth factor (CTGF) is a secreted, heparin-binding, and extracellular matrix associated protein shown to stimulate many of the cellular events underlying fibrosis. Previous investigations have revealed that myocardial CTGF is substantially induced in ischaemic heart failure, particularly in the ischaemic and peri-ischaemic region. The purpose of the present study was to investigate to what extent myocardial induction of CTGF is a general response to congestive heart failure (CHF) and to what extent CTGF is a decisive effector of fibrosis. METHODS: Experimental heart failure in pigs was induced by rapid pacing at 220-240 beats min(-1) for 3 weeks (CHF pigs; n = 12). RESULTS: The CHF pigs exhibited significant left ventricular (LV) dilatation, reduced contractility, and increased cardiac filling pressures. Northern blot analysis demonstrated that myocardial CTGF mRNA levels in CHF pigs were fivefold higher (P < 0.05) than those in control pigs (n = 10). Similar elevations of immunoreactive CTGF (sixfold; P < 0.05) were observed in myocardial tissue samples prepared for Western blot analysis. Immunohistochemical analysis of myocardial tissue sections revealed predominant expression in interstitial and perivascular fibroblasts and endothelial cells. Myocardial procollagen alpha1(I) mRNA levels were also significantly elevated (sixfold; P < 0.05) in CHF pigs compared with controls, whereas myocardial tissue contents of collagen were not statistically different between the groups. CONCLUSION: Induction of myocardial CTGF in heart failure is not just a response to ischaemia, but rather a general response to evolving heart failure. Yet, induction of myocardial CTGF was clearly not a sufficient effector of fibrosis.     

慢性心衰大鼠下丘脑室旁核瞬时外向钾通道蛋白Kv4.2和Kv4.3低表达促进肾交感神经兴奋性

 目的: 观察慢性心衰大鼠下丘脑室旁核内瞬时外向钾通道蛋白Kv4.2和Kv4.3的变化及其对交感神经活性的影响。方法: 采用冠状动脉左前降支结扎术建立大鼠心衰模型或假手术模型,造模4周后超声心动图测定心功能;酶联免疫吸附法测定血浆去甲肾上腺素(NE)及血清N端前脑钠肽(NT-proBNP)含量;Western blot和real-time PCR法测定室旁核内Kv4.2和Kv4.3的表达情况;室旁核部位注射钾通道阻滞剂4-氨基吡啶(4-AP),电生理记录仪记录血压、心率和肾交感神经放电的变化。结果: 与假手术组比,心衰组大鼠心功能明显降低,血浆NE及血清NT-proBNP明显升高,室旁核内Kv4.2和Kv4.3表达明显下调;注射4-AP后导致血压、心率和交感神经放电升高,但心衰组的升高幅度小于假手术组。结论: 心力衰竭时室旁核内Kv4.2和Kv4.3表达下调并伴有交感神经放电增加,促进心衰进展。     

Induction of myocardial connective tissue growth factor in pacing‐induced heart failure in pigs

Aims: Connective tissue growth factor (CTGF) is a secreted, heparin‐binding, and extracellular matrix associated protein shown to stimulate many of the cellular events underlying fibrosis. Previous investigations have revealed that myocardial CTGF is substantially induced in ischaemic heart failure, particularly in the ischaemic and peri‐ischaemic region. The purpose of the present study was to investigate to what extent myocardial induction of CTGF is a general response to congestive heart failure (CHF) and to what extent CTGF is a decisive effector of fibrosis. Methods: Experimental heart failure in pigs was induced by rapid pacing at 220–240 beats min^?1 for 3 weeks (CHF pigs; n = 12). Results: The CHF pigs exhibited significant left ventricular (LV) dilatation, reduced contractility, and increased cardiac filling pressures. Northern blot analysis demonstrated that myocardial CTGF mRNA levels in CHF pigs were fivefold higher (P < 0.05) than those in control pigs (n = 10). Similar elevations of immunoreactive CTGF (sixfold; P < 0.05) were observed in myocardial tissue samples prepared for Western blot analysis. Immunohistochemical analysis of myocardial tissue sections revealed predominant expression in interstitial and perivascular fibroblasts and endothelial cells. Myocardial procollagen α1(I) mRNA levels were also significantly elevated (sixfold; P < 0.05) in CHF pigs compared with controls, whereas myocardial tissue contents of collagen were not statistically different between the groups. Conclusion: Induction of myocardial CTGF in heart failure is not just a response to ischaemia, but rather a general response to evolving heart failure. Yet, induction of myocardial CTGF was clearly not a sufficient effector of fibrosis.     

RhoA经基质金属蛋白酶-3、-9通路介导心力衰竭大鼠心肌重塑及心功能恶化

目的:探讨RhoA、Rho激酶、基质金属蛋白酶家族(MMPs)MMP-3、MMP-9表达与心肌重塑及心功能损害的关系。方法:建立假手术组及心力衰竭大鼠(造模12周及20周)模型。应用Nikon 4多导生理记录仪检测血液动力学指标以评价心功能情况,心肌肥厚指数及H-E染色评价心肌重塑情况,并采用RT-PCR方法检测各组大鼠心肌组织RhoA、Rho激酶及MMP-3、MMP-9基因表达。结果:造模20周、造模12周心力衰竭组大鼠与假手术组大鼠对比,随心肌重塑加重、心功能恶化,RhoA、Rho激酶及MMP-3、MMP-9基因表达显著增加,且直线相关分析结果显示RhoA基因表达与Rho激酶、MMP-3、MMP-9基因表达呈正相关趋势。结论:RhoA可能通过刺激MMP-3、MMP-9的表达引起细胞外基质结构发生改变,引起心肌重塑和心功能恶化。     

Hyperoside protects against heart failure-induced liver fibrosis in rats

Heart failure (HF) is an end-stage of various serious cardiovascular diseases, which causes liver injury. Hyperoside has been reported to exert protective effect on liver injury and fibrosis. However, the role and related mechanisms of hyperoside in HF-induced liver fibrosis are still unclear. In the current study, we established a model of HF via aortocaval fistula (ACF) in rats in vivo. Hyperoside treatment in ACF rats increased cardiac output, the maximum peak rate of rise/fall in left ventricular pressure (+dP/dt, -dP/dt) and LV ejection fraction (LVEF), decreased LV end-systolic pressure (LVESP), LV end-diastolic pressure (LVEDP) and LV end-systolic volume (LVESV), and reduced heart weight/body weight ratio in a dose-dependent manner. Moreover, hyperoside could attenuate liver fibrosis and injury in ACF rats, as evidenced by reduction of fibrosis area and hydroxyproline content, amelioration of edema and degeneration of liver cell vacuoles, and inhibition of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels. Further, α-smooth-muscle actin (α-SMA), collagen I, profibrotic factor-connective tissue growth factor (CTGF), matrix metalloproteinase-2 (MMP2) and MMP9 levels were down-regulated in hyperoside-treated ACF rats. Additionally, hyperoside inhibited the activation of TGF-β1/Smad pathway. Finally, we confirmed that hyperoside suppressed TGF-β1-mediated hepatic stellate cell activation in vitro. Collectively, hyperoside showed a suppressive role in HF-induced liver fibrosis and injury.     

Medroxyprogesterone acetate aggravates oxidative stress and left ventricular dysfunction in rats with chronic myocardial infarction

The role of estrogens during myocardial ischemia has been extensively studied. However, effects of a standard hormone replacement therapy including 17β-estradiol (E2) combined with medroxyprogesterone acetate (MPA) have not been assessed, and this combination could have contributed to the negative outcomes of the clinical studies on hormone replacement. We hypothesized that adding MPA to an E2 treatment would aggravate chronic heart failure after experimental myocardial infarction (MI). To address this issue, we evaluated clinical signs of heart failure as well as left ventricular (LV) dysfunction and remodeling in ovariectomized rats subjected to chronic MI receiving E2 or E2 plus MPA. After eight weeks MI E2 showed no effects. Adding MPA to E2 aggravated LV remodeling and dysfunction as judged by increased heart weight, elevated myocyte cross-sectional areas, increased elevated left ventricle end diastolic pressure, and decreased LV fractional shortening. Impaired LV function in rats receiving MPA plus E2 was associated with increased cardiac reactive oxygen species generation and myocardial expression levels of NADPH oxidase subunits. These results support the interpretation that adding MPA to an E2 treatment complicates cardiovascular injury damage post-MI and therefore contributes to explain the adverse outcome of prospective clinical studies.     

Cardiovascular ultrasound: applications for the assessment of cardiac function

Congestive heart failure(CHF) is usually associated with impaired left ventricular(LV) systolic function, and thus, the measurement of systolic function is an essential component of the evaluation of any patients with known or suspected cardiac disease. Among many parameters, most frequently used are LV percent fractional shortening and ejection fraction(EF), which can be easily measured from an M-mode echocardiogram. However, these M-mode measurements may be inaccurate in patients with asymmetrical LV due to myocardial infarction, right ventricular overload or sigmoid septum. Especially in such cases, EF should be measured using two-dimensional echocardiography. Usually, LV volumes and EF are calculated using the disc-summation method through the manual tracing of apical two-chamber and four-chamber echocardiograms. On the other hand, it has been recognized that congestive heart failure may arise in the absence of any systolic dysfunction and CHF due to systolic dysfunction never occurs in the absence of concomitant diastolic dysfunction. Although the analysis of pulsed-Doppler transmitral flow velocity has been most widely used for the noninvasive assessment of LV diastolic function, an increase in left atrial pressure during CHF can pseudonormalize an abnormal flow pattern and mask LV diastolic dysfunction. Recently, we proposed a new index for assessing LV diastolic function, flow propagation velocity, which can be measured with color M-mode Doppler echocardiography and baseline-shift technique. Recent studies have shown that the flow propagation velocity is a unique noninvasive parameter of LV diastolic function which can accurately detect the diastolic impairment in patients with different types of cardiac diseases with various loading conditions.     

基质金属蛋白酶及其组织型抑制剂活性及表达失衡与高血压性左心室重塑的关系

目的： 探讨慢性压力负荷增高时，大鼠左心室（LV）基质金属蛋白酶（MMPs）/组织型基质金属蛋白酶抑制剂（TIMPs）失衡与LV重塑的关系。方法：40只6周龄雄性卒中易感性自发性高血压大鼠（SHR-SPs）作为研究对象，10只同周龄雄性Wistar-Kyoto（WKY）大鼠作为对照。6个月后，以Millar压力容积导管评价2组大鼠的在体LV血流动力学，并对2组大鼠的心脏进行组织病理学、明胶酶谱和免疫印迹法分析。结果：反映LV收缩与舒张功能的血流动力学参数在2组间有显著差异（P＜0.05）；SHR-SPs心脏胶原容积分数、血管周胶原面积/管腔面积、心肌横断面积、心室壁动脉中膜面积/管腔面积均增高（P＜0.05）；心肌MMP-2活性、蛋白含量及TIMP-1蛋白含量在SHR-SPs中明显增高（P＜0.05）。结论：慢性压力超负荷能够导致心脏细胞外基质代谢失调及MMPs/TIMPs系统失衡，继而产生心室腔扩张、LV收缩与舒张功能障碍。     

大鼠阿霉素慢性心衰模型的制备与心衰指标的判定

目的探讨大鼠阿霉素(adrinmycin,ADR)慢性心衰(chronicheartfailure,CHF)模型的制备与心衰指标的判定。方法采用ADR给大鼠隔日腹腔注射制作慢性心衰模型,并通过行为体征观察、初体重和终体重、心重及心体比、心功能测定、心、肝和肺病理学光镜以及心肌病理学电镜观察进行心衰指标的判定。结果模型组大鼠萎靡不振、活动、进食减少、呼吸加快、体温下降、体重明显减轻,且左室内压、压力升高最大速率(±dp/dtmax)、心率明显降低,心脏病理学改变明显,基本符合Bishop关于慢性心衰CHF动物模型制作的标准,说明用ADR方法复制CHF模型是成功的。更贴近临床心肌病性CHF的病理生理过程。结论用阿霉素制作CHF模型技术方法容易控制,心衰指标符合标准。     

Endotoxinemia and systemic inflammation in pathogenesis of chronic heart failure

Large intestine microbiocenosis, levels of endotoxinemia, tumor necrosis factor alpha, C-reactive protein, sE-selectin, matrix metalloproteinase-9 (MMP) and tissue inhibitor of metalloproteinases-4 (TIMP) in chronic heart failure (CHF) patients was studied. Association of dysbiosis and endotoxinemia levels increase, systemic inflammation activation and an imbalance of MMP-TIMP system with progression of CHF has been shown. It can be a reason of a myocardium extracellular matrix structure disturbance and heart remodeling at CHF.     

The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model

Congestive heart failure (CHF) is a chronic disease with a high mortality rate. Managing CHF patients has been one of the most severe health care problems for years. Scaffold materials have been predominantly investigated in acute myocardial infarction (MI) studies and have shown promising improvement in LV function. In this study we examined whether surface modification of a biomaterial can influence the myocardial microenvironment and improve myocardial function in a rodent model of ischemic cardiomyopathy. In vitro cell culture and in vivo rat studies were performed. RGD peptides conjugated to alginate improved human umbilical vein endothelial cell (HUVEC) proliferation and adhesion when compared to a non-modified alginate group. Injection of the alginate hydrogel into the infarct area of rats 5 weeks post-MI demonstrated that both modified and non-modified alginate improve heart function, while LV function in the control group deteriorated. Both the RGD modified alginate and non-modified alginate increased the arteriole density compared to control, with the RGD modified alginate having the greatest angiogenic response. These results suggest that in situ use of modified polymers may influence the tissue microenvironment and serve as a potential therapeutic agent for patients with chronic heart failure.     

心衰大鼠心肌核因子-κB活化及其与心肌细胞凋亡的关系

目的:探讨核因子-κB(NF-κB)活化与充血性心力衰竭(CHF)大鼠心肌细胞凋亡发生、发展的关系及其对Fas和Fas配体(FasL)表达的调控作用。方法:以假手术组为对照,观察雄性Wistar大鼠心肌梗死(MI)后2周、4周及8周的血流动力学指标、心肌细胞凋亡指数、Fas、FasL、Bcl-2和κB抑制蛋白的表达及NF-κB核结合活性的改变。结果:MI后心肌细胞凋亡指数、Fas及FasL表达水平进行性升高,Bcl-2的mRNA表达下调;κB抑制蛋白水平逐渐降低,而NF-κB活性逐渐增高。结论:心肌细胞凋亡在MI后CHF发生、发展过程中起着重要作用,NF-κB活化启动Fas和FasL基因转录,Fas和FasL表达上调、Bcl-2表达下降介导大鼠MI后心肌细胞凋亡的发生。     

Functional and biochemical analyses of isolated rat hearts in renal and reversed renal hypertension

The present study evaluates cardiac function, plasma renin activity (PRA) and left ventricular (LV) myosin isoenzymes in untreated two-kidney, one-clip Goldblatt hypertensive rats (2KIC) and in 2KIC treated with felodipine and metoprolol. Normotensive rats (NCR) and another group of 2KIC, in which the renal artery constriction was removed (UC-2KIC), were also investigated. Cardiac performance was assessed by means of a working heart perfusion device, allowing also for measurements of myocardial oxygen consumption. Following antihypertensive therapy and unclipping, blood pressure became close to normotensive levels. PRA remained equally elevated in treated and untreated 2KIC, but became practically normalized after unclipping. Relative LV weight in 2KIC increased 74% above that in NCR but in treated 2KIC increased by only 20%. In UC-2KIC LV hypertrophy became reversed, LV weight/body being about the same as in treated 2KIC. In treated 2KIC, coronary resistance at maximal dilatation was significantly reduced, implying prevention of hypertensive, structural coronary vascular changes, and optimal LV function was improved markedly in the lower range of perfusion pressures compared with untreated 2KIC. When, however, the hearts were challenged at a high pumping resistance (perfusion pressure), LV function was similar in untreated and treated 2KIC. Myocardial oxygen consumption for given levels of stroke work was significantly lower in treated than in untreated 2KIC. The myosin isoenzyme pattern in the LV of 2KIC was shifted, with significantly higher amounts of VM-3 than in NCR. This shift was normalized by antihypertensive therapy or by unclipping. In conclusion, antihypertensive therapy with felodipine and metoprolol prevents the development of coronary vascular and left ventricular hypertrophy in 2KIC. This may contribute to enhance cardiac performance at low aortic pressure. The lack of improvement in optimal cardiac performance (at high aortic pressure) implies that the hypertensive state per se, rather than extent of pressure elevation, cardiac hypertrophy, or changes of LV isoenzymes, determines the reduced cardiac function in renal hypertensive rats (Friberg & Nordborg 1986).     

黄芪甲苷对慢性心衰大鼠心肌纤维化及能量代谢的影响

目的:研究黄芪甲苷对慢性心衰大鼠心肌纤维化的影响,初步探讨其具体机制。方法:采用腹主动脉缩窄法(AAC)建立大鼠慢性心衰模型,建模成功后随机分为模型组、缬沙坦组及黄芪甲苷组,另建立假手术组。缬沙坦组和黄芪甲苷组分别给予2 mg·kg~(-1)·d~(-1)的缬沙坦及30 mg·kg~(-1)·d~(-1)的黄芪甲苷灌胃,假手术组及模型组给予生理盐水灌胃。8周后收集心脏结构及血流动力学参数,留取心肌染色后观察心肌细胞形态学变化Western blot和RT-qPCR检测长链脂酰辅酶A脱氢酶(LCAD)、6-磷酸果糖激酶1(PFK1)的蛋白及mRNA表达情况。结果:与假手术组相比,模型组大鼠的左室质量指数(LVMI)、胶原容积分数(CVF)、左室后壁厚度(LVPWD)、PFK1蛋白及mRNA表达均升高(P0.05),LCAD蛋白及mRNA表达均下降(P0.05)。与模型组相比,缬沙坦组及黄芪甲苷组LVMI、CVF、LVPWD、PFK1蛋白及mRNA表达均下降(P0.05),LCAD蛋白及mRNA表达升高(P0.05)。结论:黄芪甲苷可以抑制慢性心衰大鼠心肌纤维化,其机制可能是通过上调LCAD、下调PFK1、纠正能量代谢异常实现的。     

室旁核内花生四烯酰乙醇胺对心衰大鼠的心脏功能和交感神经活动的影响

目的:探究慢性心衰大鼠下丘脑室旁核(PVN)内花生四烯酰乙醇胺(AEA)对心脏功能和交感神经活动的影响。方法:采用冠状动脉结扎法构建大鼠心衰模型,超声心动图检测心功能;PVN内连续4周分别灌注AEA、钙/钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)选择性抑制剂KN-93、瞬时受体电位香草酸亚型1(TRPV1)通道特异性阻断剂辣椒平(CPZ)、Ca~(2+)螯合剂BAPTA-AM和小电导钙激活钾通道(SK通道)阻断剂apamin后,检测交感驱动及心功能指标;同时采用不同浓度AEA孵育NG108细胞,荧光测定法检测细胞内钙离子浓度([Ca~(2+)]_i);Western blot检测CaMKII、SK_2及磷酸化TRPV1蛋白水平。结果:与假手术组相比,心衰组左心室舒张末期压(LVEDP)明显升高,左室压力最大上升、下降速率(±dp/dt_(max))和射血分数(EF)明显下降;PVN内AEA含量、[Ca~(2+)]_i及CaMKII、SK_2和磷酸化TRPV1蛋白水平均显著降低;与溶剂组相比,心衰组PVN内灌注AEA可显著降低心衰大鼠死亡率和交感驱动指标,并改善心功能;然而,PVN内分别灌注KN-93、CPZ、BAPTA-AM和apamin均显著增强交感驱动指标并恶化心功能;AEA可剂量依赖性增加NG108细胞内[Ca~(2+)]_i及CaMKII、SK_2和磷酸化TRPV1蛋白水平。结论:室旁核内CaMKII/TRPV1/Ca~(2+)/SK_2信号通路可能参与了AEA对心衰大鼠心脏功能和交感神经活动的影响。     

A dynamic model of total chronic heart failure in rats

A dynamic model ofbiventricular chronic heart failure (CHF) induced by fractional introduction of silicon oil into the pleural cavity in rats is proposed. Silicon oil led to enlargement of the heart, myocardial hypertrophy of both ventricles, considerable pulmonary and hepatic congestion due to circulatory failure, decreased stroke volume and cardiac output, increased peripheral vascular resistance, changes in the activity of sympathoadrenal system of the heart and blood. The severity of the induced CHF varied with the dose and number of silicon oil administrations.     

Effects of Beta-Receptor Blockade and Angiotensin II Type I Receptor Antagonism in Isoproterenol - Induced Heart Failure in the Rat

The aim of this study was to examine the effects of both angiotensin II type I receptor antagonism using losartan (LOS) and beta-receptor blockade by metoprolol (MP) in isoproterenol-induced cardiac injury in the rat. Two weeks after isoproterenol (ISO) application, 90 ISO and 30 control (CTRL) rats were examined. ISO rats were treated for two weeks with either LOS, MP, or vehicle (n = 30 each group). Compared to CTRL, ISO induced left ventricular hypertrophy (LVH), fibrosis, and overexpression of extracellular matrix proteins. LOS significantly attenuated these changes. MP only reduced LVH, but exerted no effect on structural alterations. LV end-diastolic and mean right atrial pressures were significantly increased in the ISO group and normalized in the LOS and MP group. Mean aortic blood flow velocity was significantly decreased in the ISO group and unaltered in the LOS and MP group versus CTRL. Blood pressure was decreased in ISO and LOS rats. MP treatment had no effect on blood pressure, but significantly lowered heart rate. Isoproterenol induced mild heart failure. Losartan and metoprolol applications in ISO-treated rats were highly effective in attenuating hemodynamic alterations and LVH. Early application of losartan 24 hours after isoproterenol-induced cardiac injury revealed significant beneficial effects on myocardial structure.     

Functional role of endogenous endothelin-1 in congestive heart failure treated with angiotensin II receptor antagonist

Interactions between angiotensin (ANG) II and endothelin (ET)-1 receptor transduction pathways have been unclear in congestive heart failure (CHF). Therefore the objects of this study are, in CHF, whether production of ET-1 is modulated by ANG II and/or whether hemodynamic effects of endogenous ET-1 are modulated by ANG II. Twelve dogs were randomly assigned to two groups: untreated (n = 6) and treated with ANG II type 1 (AT1) receptor antagonist (TCV116, 1.5 mg/kg/d) (n = 6). After rapid ventricular pacing (240 bpm) for 4 weeks, plasma and cardiac ET-1 levels were compared between the two groups. Acute hemodynamic effects of a nonspecific ET(A&B) receptor antagonist, TAK044 (3 mg/kg plus 3 mg/kg/h i.v.) were examined in both groups by a conductance catheter and a micromanometer. After 4 weeks of pacing, plasma and cardiac tissue ET-1 levels were elevated in both groups to a similar degree. In the group treated with TCV116, TAK044 produced an increase in stroke volume and a decrease in total systemic resistance; heart rate was unchanged. The time constant of left ventricular (LV) relaxation was significantly decreased. The slope of LV end-systolic pressure-volume relation (E(ES)) was increased (p < 0.05), indicating an increased LV contractility. Thus endogenous ET-1 produces an arterial vasoconstriction and impairs LV contractility and relaxation in CHF with AT1 receptor antagonism. These hemodynamic responses to TAK044 in CHF treated with TCV116 were similar in untreated CHF. These results suggest that the production of ET-1 and the cardiac effects of endogenous ET-1 in CHF may be unaffected by ANG II acting through AT1 receptors.     

Ontogeny of enhanced decorin levels and distribution within myocardium of failing hearts

The proteoglycan, decorin, is a regulator of collagen fibril organization and its resulting functional properties. The temporal and spatial expression of decorin during the progression to heart failure is not well understood and may play a significant role in extracellular matrix remodeling. Decorin and types I and III collagen levels were measured in male Spontaneously Hypertensive Heart Failure (SHHF) and control Wistar-Furth rats at 2 and 8 mo, and at congestive heart failure (CHF). Decorin levels increased in the SHHF rats relative to the control rats in CHF. Type I collagen levels increased while type III levels decreased in the SHHF rats in CHF relative to the age matched controls. The SHHF rats have 48 and 45 KDa isoforms of the decorin core protein expressed at all ages while control Wistar-Furths produced only a 45 KDa form. Decorin was localized in the outer ventricle wall but during CHF, decorin was expressed throughout the ventricular myocardium. Immunogold localization of decorin demonstrated an increased distribution of decorin along the myocardium collagen fibrils at CHF. The enhanced expression and greater distribution of decorin may be linked to extracellular matrix remodeling which occurs with the development of heart failure.     

Ontogeny of Enhanced Decorin Levels and Distribution Within Myocardium of Failing Hearts

The proteoglycan, decorin, is a regulator of collagen fibril organization and its resulting functional properties. The temporal and spatial expression of decorin during the progression to heart failure is not well understood and may play a significant role in extracellular matrix remodeling. Decorin and types I and III collagen levels were measured in male Spontaneously Hypertensive Heart Failure (SHHF) and control Wistar-Furth rats at 2 and 8 mo, and at congestive heart failure (CHF). Decorin levels increased in the SHHF rats relative to the control rats in CHF. Type I collagen levels increased while type III levels decreased in the SHHF rats in CHF relative to the age matched controls. The SHHF rats have 48 and 45 KDa isoforms of the decorin core protein expressed at all ages while control Wistar-Furths produced only a 45 KDa form. Decorin was localized in the outer ventricle wall but during CHF, decorin was expressed throughout the ventricular myocardium. Immunogold localization of decorin demonstrated an increased distribution of decorin along the myocardium collagen fibrils at CHF. The enhanced expression and greater distribution of decorin may be linked to extracellular matrix remodeling which occurs with the development of heart failure.