Salutary effects of attenuation of angiotensin II on coronary perivascular fibrosis associated with insulin resistance and obesity

Zaman, A.K.M. Tarikuz; Fujii, Satoshi; Goto, Daisuke; Furumoto, Tomoo; Mishima, Tetsuya; Nakai, Yukihito; Dong, Jie; Imagawa, Shogo; Sobel, Burton E.; Kitabatake, Akira

doi:10.1016/j.yjmcc.2004.05.006

Cited by 63 publications

(49 citation statements)

References 39 publications

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“…Likewise, collagen ␣ 1 protein content was modestly increased in the myocardium of female rats fed a high-fat diet but did not reach statistical significance. Collectively, these data were consistent with previous studies demonstrating the presence of a reactive fibrotic response in the myocardium of various experimental animal models of obesity (Zaman et al, 2004;Carroll and Tyagi, 2005). However, the present study has revealed that the reactive fibrotic response in the heart of female rats fed a high-fat diet represents an early maladaptive event independent of overt obesity, hyperlipidemia, and hyperglycemia.…”

Section: High-fat Diet and Cardiac Fibrosis 965supporting

confidence: 93%

“…However, the present study has revealed that the reactive fibrotic response in the heart of female rats fed a high-fat diet represents an early maladaptive event independent of overt obesity, hyperlipidemia, and hyperglycemia. Furthermore, the induction of putative profibrotic peptides in the heart of obese animals was implicated in reactive fibrosis (Zaman et al, 2004;Carroll and Tyagi, 2005). Unexpectedly, a significant down-regulation of transforming growth factor-␤ 3 mRNA was observed in the LV of rats fed a high-fat diet.…”

Section: High-fat Diet and Cardiac Fibrosis 965mentioning

confidence: 99%

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Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol

Aubin

Lajoie²,

Clement³

et al. 2008

J Pharmacol Exp Ther

100

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It remains presently unknown whether vascular reactivity is impaired and whether maladaptive cardiac remodeling occurs before the onset of overt obesity and in the absence of hyperlipidemia. Normal female rats were fed a high-fat diet for 8 weeks and were associated with a modest nonsignificant increase of body weight (standard diet, 300 Ϯ 10, versus high-fat diet, 329 Ϯ 14 g) and a normal plasma lipid profile. In rats fed a high-fat diet, systolic (171 Ϯ 7 mm Hg) and diastolic blood pressures (109 Ϯ 3) were increased compared to a standard diet (systolic blood pressure, 134 Ϯ 8; diastolic blood pressure, 96 Ϯ 5 mm Hg), and acetylcholine-dependent relaxation of isolated aortic rings (high-fat diet, 22 Ϯ 5%, versus standard diet, 53 Ϯ 8%) was significantly reduced. Furthermore, perivascular fibrosis was detected in the heart of rats fed a high-fat diet. The exogenous addition of resveratrol (trans-3,5,4Ј-trihydroxystilbene) (0.1 M) to aortic rings isolated from rats fed a high-fat diet restored acetylcholine-mediated relaxation (47 Ϯ 9%). The administration of resveratrol (20 mg/kg/day for 8 weeks) to rats fed a high-fat diet prevented the increase in blood pressure and preserved acetylcholine-dependent relaxation of isolated aortic rings. However, resveratrol therapy failed to attenuate the perivascular fibrotic response. These data have demonstrated that a high-fat diet fed to normal female rats can elicit a hypertensive response and induce perivascular fibrosis before the development of overt obesity and in the absence of hyperlipidemia. Resveratrol therapy can prevent the hypertensive response in female rats fed a high-fat diet but is without effect on the progression of perivascular fibrosis.

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Section: High-fat Diet and Cardiac Fibrosis 965supporting

confidence: 93%

Section: High-fat Diet and Cardiac Fibrosis 965mentioning

confidence: 99%

Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol

Aubin

Lajoie²,

Clement³

et al. 2008

J Pharmacol Exp Ther

100

View full text Add to dashboard Cite

show abstract

“…Increased cardiac JNK and AP-1 DNAbinding activities in stroke-prone hypertensive rats were reduced by losartan. Levels of phospho-p46JNK and phospho-p55JNK were elevated in the LVs of obese mice (Zaman et al 2004). ACEI and angiotensin II receptor blockers (ARB) decreased the activation of these JNK isoforms.…”

Section: Discussionmentioning

confidence: 99%

Early blood pressure-independent cardiac changes in diabetic rats

Landau¹,

Chayat

Zucker³

et al. 2008

Journal of Endocrinology

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Cardiac remodeling is a key event in both diabetic and hypertensive heart diseases. In the present study, we investigated early myocardial changes in an animal model, the male Sabra rat model (SBH/y) of salt-induced hypertension-rendered diabetic with streptozotocin. Control non-diabetic (C), diabetic (D), and D or C rats made hypertensive by salt loading (DS or CS) were studied after 6 weeks. M-mode echocardiography revealed that left ventricular internal dimension during diastole and systole were significantly increased in D and DS, but not in C or CS. Concurrently, we found in D and DS an increase in cardiac b-myosin heavy chain, atrial natriuretic peptide, skeletal a-actin mRNA, type III collagen, and transforming growth factor-b.Myocardial angiotensin-converting enzyme (ACE) mRNA levels were increased while ACE2 mRNA levels were decreased in both D and DS groups. Cardiac angiotensin-1 (AT1) receptor protein levels were unchanged but the levels of phosphorylated (p) ERK and Jun-NH 2 -protein kinase (JNK) were increased in D and DS. In conclusion, we detected early cardiac changes in diabetic rats that were unrelated to hypertension. The increase in ACE, the decrease in ACE2, and the increase in cardiac pERK and pJNK suggest an increase in free angiotensin II and AT1R signaling in the diabetic myocardium as a possible mechanism contributing to cardiac remodeling in diabetes.

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“…The fibrogenic effect of angiotensin II is largely accounted for by the upregulation of TGF-b1 via the angiotensin II receptor type 1 activation. 28 TGF-b1 and its downstream mediator, connective tissue growth factor, both enhance fibrous tissue formation and diminish its degradation, hence increasing perivascular and interstitial fibrosis, including also myocardium.…”

Section: 12mentioning

confidence: 99%

Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function

et al. 2008

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Background: Myocardial fibrosis is one of the mechanisms underlying left ventricular (LV) dysfunction in obese patients and may result from dysregulation of extracellular matrix (ECM) turnover. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) represent a regulatory system playing a crucial role in ECM metabolism. Objectives: We sought to assess plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in obese young women and to evaluate the association between MMP/TIMP system components and LV function in this population. Design: Prospective, cross-sectional study. Setting: University hospital. Patients: Seventy-one women aged o35 years with body mass index 430 kg m À2 and 30 healthy slim female controls. Main outcome measures: Plasma MMP-2, MMP-9, TIMP-1 and TIMP-2 measurements and echocardiographic studies, including LV strain/strain rate evaluation. Results: We demonstrated increased levels of MMP-9 and TIMP-1 and decreased MMP-2 in the obese population. LV dysfunction shown in patients with obesity was characterized by significantly lower values of strain/strain rate parameters. Plasma MMP-2 correlated positively and TIMP-1 negatively with systolic strain (r ¼ 0.39, Po0.001 and r ¼ À0.40, Po0.001, respectively), peak systolic strain rate (r ¼ 0.38, Po0.001 and r ¼ À0.27, Po0.03, respectively) and peak early diastolic strain rate (r ¼ 0.40, Po0.001 and r ¼ À0.24, Po0.05, respectively). Plasma MMP-2, fasting insulin and body mass index proved the only independent determinants of strain/strain rate parameters of LV systolic and diastolic performance in obese subjects. Conclusions: In premenopausal obese women (1) plasma MMP/TIMP profile is altered, (2) abnormalities of LV function are related to the changes in the MMP/TIMP system that might promote attenuated ECM degradation, mainly to the downregulation of MMP-2.

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Salutary effects of attenuation of angiotensin II on coronary perivascular fibrosis associated with insulin resistance and obesity

Cited by 63 publications

References 39 publications

Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol

Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol

Early blood pressure-independent cardiac changes in diabetic rats

Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function

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