Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion.
OBJECTIVE
The aim of the study was to assess whether and how the high-cholesterol diet (HCD)-related worsening of heart failure differs between coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced myocardial infarction (MI).


BACKGROUND
An HCD, a risk factor for coronary artery disease, also worsens ischemic heart failure. Although accelerated coronary plaque formation may be a cause of this, other mechanism(s), such as its effects through the coronary microcirculation, remain to be clarified.


METHODS
In rats fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed left ventricular (LV) function by echocardiography and myocardial inflammation by histopathology. In the CS groups, CS severity by histopathology, myocardial perfusion by microspheres, myocardial protein kinase C (PKC) translocation by Western blotting, and myocardial endothelial nitric oxide (NO) function were also investigated by the in vitro myocardial oxygen consumption method.


RESULTS
Coronary stenosis impaired myocardial endothelial NO function and reduced coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation, myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By itself, HCD greatly augmented such CS-induced myocardial abnormalities without modulating the CS severity. Such detrimental effects of HCD were ameliorated by supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast, MI-induced heart failure was not aggravated by HCD.


CONCLUSIONS
The CS-induced ischemic myocardium seems to be more susceptible to the pro-inflammatory effect of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and remodeling via modification of the coronary circulation downstream of the epicardial CS site, partly through impairment of endothelial NO.
Yaoita
Hiroyuki
H
First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan.
Yoshinari
Kazuyuki
K
Maehara
Kazuhira
K
Sando
Masahito
M
Watanabe
Kenichi
K
Maruyama
Yukio
Y
D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D023921:Coronary Stenosis / Q000150:complications*; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology; D006333:Heart Failure / Q000209:etiology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling
D002791:Cholesterol, Dietary; D019001:Nitric Oxide Synthase