To begin to dissect atherogenesis as a complex genetic disorder affected by genetic makeup and environment, we have (a) generated a reproducible mouse model of neointimal growth; (b) evaluated the effect of disruption of a single gene, endothelial nitric oxide synthase, believed to be central to intimal growth, and (c) examined the modifying effects of gender and pregnancy upon the vascular response. Cuff placement around the femoral artery causes reproducible intimal growth. We assessed the response to injury by quantitative morphometry, measuring the intimal to medial (I/M) volume ratio. In wild-type mice, cuff placement causes pronounced intimal proliferation without affecting the media, resulting in I/M ratios of 31% (SV129 males) and 27% (C57BL/6 males). eNOS mutant male mice have a much greater degree of intimal growth (I/M ratio of 70%). Female mice show less intimal response than do males, although eNOS mutant female mice still have more response than do wild-type females. Most dramatic, however, is the effect of pregnancy, which essentially abolishes the intimal response to injury, even overriding the effect of eNOS mutation. We conclude that eNOS deficiency is a genetic predisposition to intimal proliferation that is enhanced by male gender, and that may be overridden by pregnancy.
M Moroi, L Zhang, T Yasuda, R Virmani, H K Gold, M C Fishman, P L Huang
Title and authors | Publication | Year |
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Antiatherosclerotic Effects of Small-Molecular-Weight Compounds Enhancing Endothelial Nitric-Oxide Synthase (eNOS) Expression and Preventing eNOS Uncoupling
P Wohlfart, H Xu, A Endlich, A Habermeier, EI Closs, T Hübschle, C Mang, H Strobel, T Suzuki, H Kleinert, U Förstermann, H Ruetten, H Li |
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Additive effects of statin and dipyridamole on cerebral blood flow and stroke protection
HH Kim, N Sawada, G Soydan, HS Lee, Z Zhou, SK Hwang, C Waeber, MA Moskowitz, JK Liao |
Journal of Cerebral Blood Flow & Metabolism | 2008 |
Spontaneous Myocardial Infarction and Nitric Oxide Synthase
M Tsutsui, S Nakata, H Shimokawa, Y Otsuji, N Yanagihara |
Trends in Cardiovascular Medicine | 2008 |
Cardiovascular roles of nitric oxide: a review of insights from nitric oxide synthase gene disrupted mice
VW Liu, PL Huang |
Cardiovascular Research | 2008 |
Intimal hyperplasia in murine models
DY Hui |
Current drug targets | 2008 |
Diabetic eNOS knockout mice develop distinct macro- and microvascular complications
S Mohan, RL Reddick, N Musi, DA Horn, B Yan, TJ Prihoda, M Natarajan, SL Abboud-Werner |
Laboratory Investigation | 2008 |
Colchicine Inhibits Intimal Hyperplasia and Leukocyte VEGF Expression in Dogs
HM Atta, MA El-Rehany, SR Raheim, R Fouad, AM Galal |
Journal of Surgical Research | 2008 |
Translational Therapeutics of Dipyridamole
HH Kim, JK Liao |
Arteriosclerosis, thrombosis, and vascular biology | 2008 |
Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout mice:
Y XU, H ARAI, T MURAYAMA, T KITA, M YOKODE |
Chinese Medical Journal | 2008 |