Diet-induced hypercholesterolemia impaired intrinsic left ventricular function eight weeks after myocardial ischemia-reperfusion injury in mice, despite paradoxically reducing infarct size from 22.2% to 12.7%.
Does diet-induced hypercholesterolemia affect cardiac function, infarct size, and inflammation in APOE*3-Leiden mice following myocardial ischemia-reperfusion injury?
In a mouse model of ischemia-reperfusion, diet-induced hypercholesterolemia impaired long-term left ventricular function despite paradoxically reducing infarct size and myocardial inflammation.
Absolute Event Rate: 12.7% vs 22.2%
p-value: p=0.017
BACKGROUND: Hypercholesterolemia is a major risk factor for ischemic heart disease including acute myocardial infarction. However, long-term effects of hypercholesterolemia in a rodent myocardial ischemia-reperfusion injury model are unknown. Therefore, the effects of diet-induced hypercholesterolemia on cardiac function and remodeling were investigated up to eight weeks after myocardial ischemia-reperfusion (MI-R) injury which was induced in either normocholesterolemic (NC-MI) or hypercholesterolemic (HC-MI) APOE*3-Leiden mice. METHODS: Left ventricular (LV) dimensions were serially assessed using parasternal long-axis echocardiography followed by LV pressure-volume measurements. Subsequently, infarct size and the inflammatory response were analyzed by histology and fluorescence-activated cell sorting (FACS) analysis. RESULTS: Intrinsic LV function eight weeks after MI-R was significantly impaired in HC-MI compared to NC-MI mice as assessed by end-systolic pressure, dP/dtMAX, and -dP/dtMIN. Paradoxically, infarct size was significantly decreased in HC-MI compared to NC-MI mice, accompanied by an increased wall thickness. Hypercholesterolemia caused a pre-ischemic peripheral monocytosis, in particular of Ly-6Chi monocytes whereas accumulation of macrophages in the ischemic-reperfused myocardium of HC-MI mice was decreased. CONCLUSION: Diet-induced hypercholesterolemia caused impaired LV function eight weeks after MI-R injury despite a reduced post-ischemic infarct size. This was preceded by a pre-ischemic peripheral monocytosis, while there was a suppressed accumulation of inflammatory cells in the ischemic-reperfused myocardium after eight weeks. This experimental model using hypercholesterolemic APOE*3-Leiden mice exposed to MI-R seems suitable to study novel cardioprotective therapies in a more clinically relevant animal model.
Pluijmert et al. (2019) studied Myocardial ischemia-reperfusion injury (n=34). Cholesterol-enriched diet vs. Normal chow diet was evaluated on Infarct size at 8 weeks (p=0.017). Diet-induced hypercholesterolemia impaired intrinsic left ventricular function eight weeks after myocardial ischemia-reperfusion injury in mice, despite paradoxically reducing infarct size from 22.2% to 12.7%.
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