title: Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary stenosis and coronary occlusion.
abstract: 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.
authors.affiliation: First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yaoita
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yoshinari
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Maehara
authors.forename: Masahito
authors.initials: M
authors.lastname: Sando
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yukio
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: 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
chemical_list: D002791:Cholesterol, Dietary; D019001:Nitric Oxide Synthase