Post-angioplasty restenosis: the effects of exercise training

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Percutaneous transluminal coronary angioplasty (PTCA) stimulates vascular cell proliferation and migration resulting in restenosis of the revascularized artery. Exercise training (EX) following PTCA reduces stenosis diameter and increases event-free survival. Our aim was to determine the origin of the cells that migrate to form the neointima (NI) and determine if EX inhibits lesion size and alters the NI ECM composition in a porcine PTCA model. Utilizing the bromodeoxyuridine (BrdU) pulsechase technique, it was determined that few (<3%) BrdU positive cells originating from the adventitia occupy the NI. Smooth muscle myosin heavy chain (SMMHC), a SMC differentiation mark revealed uniform staining of NI cells, showing SMC primarily occupy the NI. Furthermore, EX significantly inhibited NI SMC proliferation and lesion size in the left anterior descending (LAD), but not in the left circumflex (LCX) coronary artery. EX also decreased type I collagen in the LAD but not in the LCX, implying this ECM protein participates in SMC proliferation. Total collagen was increased whereas, fibronectin was decreased in both the LAD and LCX with EX. In vitro analysis demonstrated a role for IL-6 and IL-10 to inhibit the up-regulation of collagen type I and fibronectin gene expressions in cultured SMC. Collectively, these data demonstrate a role for SMC to migrate and form the NI; whereas, EX inhibits SMC proliferation decreasing lesion size in the LAD. Furthermore, EX alters the ECM composition of the NI that may be partially mediated via the anti-inflammatory cytokines IL-6 and IL-10.