Cited by 68Cardiac Fibrosis and RemodelingRenin-Angiotensin System StudiesBlood Coagulation and Thrombosis Mechanisms

Angiotensin-Converting Enzyme Inhibition Attenuates Hypofibrinolysis and Reduces Cardiac Perivascular Fibrosis in Genetically Obese Diabetic Mice

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Zaman, A. K. M. Tarikuz, Fujii, Satoshi, Sawa, Hirotumi, Goto, Daisuke, Ishimori, Naoki, Watano, Keiko, Kaneko, Takeaki, Furumoto, Tomoo +4 more·2001·Circulation

Abstract

Background —Obesity and insulin resistance are associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathic phenomena, and increased concentrations and activity in blood of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of fibrinolysis. Methods and Results —To determine whether hypofibrinolysis in blood and tissues and its potential sequelae could be attenuated pharmacologically, we studied genetically modified obese mice. By 10 weeks of age, obese mice exhibited increases in left ventricular weight and glucose and immunoreactive insulin in blood. PAI-1 activity in blood measured spectrophotometrically was significantly elevated as well. The difference compared with values in lean controls widened by 20 weeks of age. Perivascular fibrosis in coronary arterioles and small coronary arteries was evident in obese mice 10 and 20 weeks of age, paralleling increases in PAI-1 and tissue factor expression evident by immunohistochemical image analysis, in situ hybridization, and reverse transcription–polymerase chain reaction. Inhibition of ACE activity initiated in obese mice 10 weeks of age and continued for 20 weeks arrested the increase in PAI-1 activity in blood and in cardiac PAI-1 and tissue factor mRNA as well as coronary perivascular fibrosis. Conclusions —Thus, inhibition of proteo(fibrino)lysis and augmented tissue factor expression in the heart precede and may contribute to the coronary perivascular fibrosis seen with obesity and insulin resistance. Furthermore, inhibition of ACE activity can attenuate all 3 phenomena.

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Crossref · 10.1161/01.cir.103.25.3123

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  • In ob/ob mice, fibrosis occurs mainly in the coronary perivascular region.

    “In ob/ob mice, fibrosis occurs mainly in the coronary perivascular region (391, 392).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [392]

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Research works printed but not linked: 4

  1. Botker HE, Moller N, Ovesen P, et al. Insulin resistance in microvascular angina. Lancet. 1993;342:136 -140.
  2. Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. J Clin Invest. 1995;95:995-1001.
  3. Sakamoto T, Woodcock-Mitchell J, Marutuka K, et al. Tumor necrosis factor regulates type-1 plasminogen activator inhibitor expression in mouse adipose cells. Am J Physiol. 1999;276:C1391-C1397.
  4. Folli F, Kahn CR, Hansen H, et al. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. J Clin Invest. 1997;100:2158 -2169.

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Authors
Zaman, A. K. M. T., Fujii, S., Sawa, H., Goto, D., Ishimori, N., Watano, K., Kaneko, T., Furumoto, T., Sugawara, T., Sakuma, I., Kitabatake, A., & Sobel, B. E.
Affiliations
University of Vermont (US)
Venue
Circulation
Published
2001-06-26
Volume
103
Issue
25
Pages
3123-3128
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W1965182744
Cited by
68
References
39
Citations by year
2026: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 1
FWCI
4.58
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Circulation (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
angiotensin-converting enzyme inhibition, hypofibrinolysis, plasminogen activator inhibitor-1, tissue factor, obesity, insulin resistance, coronary arterioles, diabetic mice, left ventricular hypertrophy, coronary disease
MeSH terms
Angiotensin-Converting Enzyme Inhibitors, Animals, Blood Glucose, Body Weight, Coronary Vessels, Diabetes Mellitus, Fibrinolysis, Fibrosis, Heart Ventricles, Immunohistochemistry, Peptidyl-Dipeptidase A, Male, Mice, Inbred C57BL, Mice, Obese, Myocardium, Obesity, Organ Size, RNA, Messenger, Thiazepines, Thromboplastin, Plasminogen Activator Inhibitor 1, In Situ Hybridization, Mice

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