Regulation of Fibrillar Collagen Gene Expression and Protein Accumulation in Volume-Overloaded Cardiac Hypertrophy

Namba, Takashi; Tsutsui, Hiroyuki; Tagawa, Hirofumi; Takahashi, Masaru; Saito, Keiko; Kozai, Toshiyuki; Usui, Makoto; Imanaka‐Yoshida, Kyoko; Imaizumi, Tsutomu; Takeshita, Akira

doi:10.1161/01.cir.95.10.2448

Cited by 65 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5). Similar results were also obtained by Namba et al (35). Treatment with Nic reduces collagen expression to that of controls (Fig.…”

Section: Discussionsupporting

confidence: 91%

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

Cox¹,

Sood²,

Hunt³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

. Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats. Am J Physiol Heart Circ Physiol 282: H1197-H1205, 2002. First published November 29, 2001 10.1152/ajpheart.00483.2001.-The hypothesis is that chronic increases in left ventricular (LV) load induce oxidative stress and latent matrix metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide (NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V fistula, 2) A-V fistula ϩ Nic, 3) sham operated, 4) sham ϩ Nic, and 5) control (unoperated); n ϭ 6 rats/group. After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed, and LV tissue homogeneates were prepared. A-V fistula caused an increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of malondialdehyde (MDA; a marker of oxidative stress) was 6.60 Ϯ 0.23 ng/mg protein and NO was 6.87 Ϯ 1.21 nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 Ϯ 2.5 nmol/l and decreased MDA to 3.54 Ϯ 0.34 ng/mg protein (P ϭ 0.005). Zymographic levels of MMP-2 were increased, as were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation. Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload. nitric oxide; malondialdehyde; collagen degradation; tissue inhibitor of metalloproteinase; arteriovenous fistula; nicotinamide; NADH oxidase; nitrotyrosine; TUNEL; cardiac ring; acetylcholine; nitroprusside; stretch; contraction; relaxation; heart failure THE EXTRACELLULAR MATRIX (ECM), particularly type I fibrillar collagen surrounding the cardiomyocytes, helps the cardiac muscle to synchronize contraction and relaxation during systole and diastole, respectively (22,53,62). To compensate for the increase in workload and to reduce the wall stress, the cardiac muscle undergoes hypertrophy. This leads to remodeling of the ECM (54). Remodelin...

show abstract

“…5). Similar results were also obtained by Namba et al (35). Treatment with Nic reduces collagen expression to that of controls (Fig.…”

Section: Discussionsupporting

confidence: 91%

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

Cox¹,

Sood²,

Hunt³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…A selective increase in collagen concentration in the right myocardium was previously observed in small animals with aortocaval fistula 9,10,15 and in human congenital heart disease with mixed pressure and volume right ventricular overload. 39 However, because of the treatment protocol and the difficulty to perform accurate dose findings in small animals, previous studies failed to observe changes in cardiac collagen in animals treated with Ang II antagonists.…”

Section: Activated Growth Factors and Ventricular Adaptation To Incrementioning

confidence: 53%

“…7 Increased collagen accumulation characterizes concentric hypertrophy of experimental pressure overload, 8 whereas no significant changes in fibrillar collagen content have been observed in experimental volume-induced eccentric hypertrophy. 9,10 The pattern of growth factor gene expression is then finally modified by the transition from hypertrophy to failure with enhanced angiotensin II (Ang II) formation and reduced IGF-I expression. 11 Thus, the expression of local growth factors appears to participate in the regulation of the type of cardiac hypertrophy and to characterize the transition to failure.…”

mentioning

confidence: 99%

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

et al. 2004

View full text Add to dashboard Cite

Abstract-Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (nϭ15) and in sham-operated animals (nϭ15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, PϽ0.05), and significant increase of myocyte length (ϩ29% at 3 months, PϽ0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (ϩ117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.

show abstract

“…However, our data are consistent with the lack of increase in LV collagen during short-term (Յ2 months) LV volume loading from aortocaval fistulae in dogs 22 and rats. [23][24][25] Also, although AR was not studied, recent reports suggest stress-induced variant expression of genes involved in ECM metabolism. 26 Our results contrast with those reported in the pressureloaded LV in which collagen hyperproduction frequently has been identified 27 and noncollagen ECM usually is not assessed.…”

Section: Discussionmentioning

confidence: 99%

Myocardial Fibrosis in Chronic Aortic Regurgitation

et al. 2002

View full text Add to dashboard Cite

Background — Myocardial fibrosis is common in patients with chronic aortic regurgitation (AR). Experimentally, fibrosis with disproportionate noncollagen extracellular matrix (ECM) elements precedes and contributes to heart failure in AR. Method and Results — We assessed [ 3 H]-glucosamine and [ 3 H]-proline incorporation in ECM, variations in cardiac fibroblast (CF) gene expression, and synthesis of specific ECM proteins in CF cultured from rabbits with surgically induced chronic AR versus controls. To determine whether these variations are primary responses to AR, normal CF were exposed to mechanical strain that mimicked that of AR. Compared with normal CF, AR CF incorporated more glucosamine (1.8:1, P =0.001) into ECM, showed fibronectin gene upregulation (2.0:1, P =0.02), and synthesized more fibronectin (2:1 by Western blot, P <0.06; 1.5:1 by affinity chromatography, P =0.02). Proline incorporation was unchanged by AR (1.1:1, NS); collagen synthesis was unaffected (type I, 0.9:1; type III, 1.0:1, NS). Normal CF exposed to cyclical mechanical strain during culture showed parallel results: glucosamine incorporation increased with strain (2.1:1, P <0.001), proline incorporation was unaffected (1.1:1, NS), fibronectin gene expression (1.6:1, P =0.07) and fibronectin synthesis (Western analysis, 1.3:1, P <0.01; chromatography, 1.9:1, NS) were upregulated. Conclusions — In AR, CF produce abnormal proportions of noncollagen ECM, specifically fibronectin, with relatively little change in collagen synthesis. At least in part, this is a primary response to strain imposed on CF by AR. Further study must relate these findings to the pathogenesis of heart failure in AR.

show abstract

Regulation of Fibrillar Collagen Gene Expression and Protein Accumulation in Volume-Overloaded Cardiac Hypertrophy

Cited by 65 publications

References 28 publications

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

Myocardial Fibrosis in Chronic Aortic Regurgitation

Contact Info

Product

Resources

About