4.5 Article

Extracellular matrix maturation in the left ventricle of normal and diabetic swine

Journal

DIABETES RESEARCH AND CLINICAL PRACTICE
Volume 59, Issue 1, Pages 1-9

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/S0168-8227(02)00178-X

Keywords

diabetes; fibrosis; interstitial space; remodeling; cross-links

Funding

  1. NHLBI NIH HHS [HL-58653] Funding Source: Medline
  2. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL058653] Funding Source: NIH RePORTER

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The main objective of this study is to determine the transmural distribution of extracellular matrix (ECM) collagen and maturation in non-diabetic and diabetic hearts. The Yucatan miniature swine heart ECM was analyzed in eight streptozotocin (STZ) induced diabetic pigs (Diabetic-Swine) and age matched normal control pigs (Nondiabetic-Swine). After 12 weeks of STZ induced diabetes, transmural biopsies were obtained from the left ventricular free wall divided into subendocardial, mid- and subepicardial layers. Collagen concentration and maturation were measured by RP-HPLC determination of hydroxyproline (Hyp) and content of hydroxylysylpyridinoline (HP) cross-links, respectively. Results showed a significant elevation in arterial glucose (P < 0.05) and reduction in arterial plasma insulin levels in the Diabetic-Swine. Hyp concentration was significantly greater (P < 0.05) in the subendocardial layers in both the Diabetic and Nondiabetic animals. The HP cross-link content was significantly greater (17%) in the Diabetic-swine subendocardial layer compared to Nondiabetic-Swine (P < 0.05), but not in other layers. In summary, the accumulation and/or increase in HP cross-link content in the Diabetic-Swine subendocardial layer suggests that myocardial fibrosis may be greater in this specific region. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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