Related Experiment Video
Updated: Aug 17, 2026
Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models
Published on: May 14, 2014
Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and remodeling induced by coronary
Hiroyuki Yaoita1, Kazuyuki Yoshinari, Kazuhira Maehara
1First Department of Internal Medicine, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan.
Insights
A high-cholesterol diet (HCD) worsens heart failure in coronary stenosis (CS)-induced ischemia but not myocardial infarction (MI). HCD exacerbates CS-induced inflammation and dysfunction, partly via impaired nitric oxide (NO) function.
Area of Science:
- Cardiovascular Research
- Dietary Impact on Heart Health
- Myocardial Pathophysiology
Background:
- High-cholesterol diet (HCD) is a risk factor for coronary artery disease and worsens ischemic heart failure.
- Mechanisms linking HCD to heart failure, including effects on coronary microcirculation, require clarification.
Purpose of the Study:
- To compare the effects of HCD on heart failure induced by coronary stenosis (CS) versus myocardial infarction (MI).
- To investigate the role of coronary microcirculation and nitric oxide (NO) function in HCD-exacerbated ischemic heart failure.
Main Methods:
- Rats were fed normal chow or HCD, followed by surgical induction of CS or MI.
- Left ventricular (LV) function, myocardial inflammation, perfusion, and endothelial NO function were assessed.
- Protein kinase C (PKC) translocation was analyzed via Western blotting.
Main Results:
- CS led to myocardial ischemia, inflammation, fibrosis, and cardiac dysfunction, which were aggravated by HCD.
- HCD exacerbated CS-induced abnormalities by impairing endothelial NO function and reducing coronary flow reserve.
- Tetrahydrobiopterin ameliorated HCD's detrimental effects in CS models; HCD did not worsen MI-induced heart failure.
Conclusions:
- Ischemic myocardium from CS is more susceptible to HCD-induced inflammation than infarcted myocardium.
- HCD aggravates LV dysfunction and remodeling in CS via coronary circulation changes, including impaired endothelial NO function.
- These findings highlight differential impacts of HCD on distinct heart failure etiologies.
Objectives:
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.
Related Concept Videos
01:26Coronary Artery Disease II: Pathophysiology
01:30Coronary Artery Disease I: Introduction
01:26Coronary Artery Disease IV: Preventive Measures
01:17Ischemic Heart Disease: Overview
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and narrowing...
01:26Atherosclerosis III: Management
01:26Imbalances in Cardiac Output
CHF can occur due to the failure of either side of the heart. Left-side failure leads to pulmonary congestion—the right side continues to send blood...