Impairment of myocardial angiogenic response in the absence of osteopontin.
OBJECTIVE
Osteopontin (OPN), increased in the heart following myocardial infarction (MI), plays an important role in post-MI remodeling. Angiogenesis, an important feature of tissue repair, begins in the infarcted myocardium within 3 days post-MI. Here, the authors studied the role of OPN in myocardial angiogenesis using wild-type (WT) and OPN knockout (KO) mice.


RESULTS
Measurement of angiogenic response using Griffonia simplicifolia lectin-1 (GSL-1) staining indicated reduced capillary density in the infarcted region of the OPN KO hearts as compared to WT hearts 7 and 14 days post-MI. Arteriolar density was lower in OPN KO hearts 14 days post-MI. The number of CD31 positive cells was also lower in the infarcted region of the OPN KO hearts as compared to WT hearts 14 days post-MI. In contrast, capillary and arteriolar densities in the noninfarcted regions of OPN KO and WT hearts were not significantly different. In vivo myocardial angiogenesis measured using Matrigel implantation in the left ventricular myocardium indicated significant decrease in the percentage of vessel-like areas in the OPN KO vs. WT hearts. Furthermore, in vitro Matrigel tube formation assay demonstrated a significant decrease in total tube length in cardiac microvascular endothelial cells (CMECs) isolated from OPN KO hearts as compared to CMECs from WT hearts. Treatment of OPN KO CMECs with purified OPN protein significantly increased total tube length, while bovine serum albumin had no effect.


CONCLUSIONS
Lack of OPN impairs myocardial angiogenic response, leading to adverse remodeling post-MI.
Zhao
Xue
X
Department of Physiology, James H. Quillen College of Medicine, James H. Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Johnson
Jennifer N
JN
Singh
Krishna
K
Singh
Mahipal
M
D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D053495:Osteopontin / Q000172:deficiency* / Q000494:pharmacology; D037121:Plant Lectins; D013194:Staining and Labeling; D020257:Ventricular Remodeling / Q000235:genetics
C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; C506896:Spp1 protein, mouse; D053495:Osteopontin