Premium
Excessive vascular smooth muscle and macrophage proliferation underlies impaired coronary collateral growth in the metabolic syndrome
Author(s) -
Hutcheson Rebecca Lynn,
Chaplin Jennifer,
Smith Erika,
Jadhav Rashmi,
Russell James C,
Rocic Petra
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.688.8
Subject(s) - proliferating cell nuclear antigen , cell growth , medicine , metabolic syndrome , endocrinology , immunohistochemistry , biology , pathology , biochemistry , obesity
Rationale Coronary collateral growth (CCG) is impaired in the metabolic syndrome. It is thought that inadequate cell proliferation is a causative factor. Pro‐angiogenic growth factors (GFs) stimulate cell proliferation. Metabolic syndrome patients and animal models exhibit elevated GF levels, but administration of GFs does not promote CCG in the metabolic syndrome. Objective To determine whether temporally inappropriate excessive cell proliferation underlies impaired CCG in the metabolic syndrome. Methods and Results Normal (SD) and metabolic syndrome (JCR) rats underwent transient, repetitive coronary artery occlusion (RI). We have previously shown that CCG was maximal at day 9 of RI in SD rats but did not occur in JCR rats. Cell proliferation was evaluated by immunohistochemistry (PCNA, Ki‐67) and Western blotting (PCNA). The increase in cell proliferation was transient in SD but greater and sustained in JCR rats. Assessment of cell cycle progression confirmed early and transient cell proliferation in SD vs. sustained proliferation in JCR rats. This was associated with accumulation of proliferating cells in the lumen of small arterioles in JCR rats, which failed to undergo outward expansion. Conclusions Excessive cell proliferation in the later stages of collateral remodeling underlies impaired CCG in the metabolic syndrome. R01 HL093052