J Nutr Biochem. , 2021., Aug 3;98:108829. doi: 10.1016/j.jnutbio.2021.108829.

Dietary flaxseed reduces Myocardial Ischemic Lesions, improves cardiac function and lowers cholesterol levels despite the presence of severe obesity in JCR:LA-cp Rats.

Abstract

Previous work has shown that dietary flaxseed can significantly reduce cardiac damage from a coronary artery ligation-induced myocardial infarction. However, this model uses healthy animals and the ligation creates the infarct in an artificial manner. The purpose of this study was to determine if dietary flaxseed can protect the hearts of JCR:LA-cp rats, a model of genetic obesity and metabolic syndrome, from naturally occurring myocardial ischemic lesions. Male and female obese rats were randomized into four groups (n = 8 each) to receive, for 12 weeks, either a) control diet (Con), b) control diet supplemented with 10% ground flaxseed (CFlax), c) a high-fat, high sucrose (HFHS) diet, or d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. In male obese rats, serum total cholesterol and LDL-C were significantly lower in CFlax compared to Con. Obese rats on HFHS exhibited increased myocardial ischemic lesions and diastolic dysfunction regardless of sex. HFlax significantly lowered the frequency of cardiac lesions and improved diastolic function in male and female obese rats compared to HFHS. Blood pressures were similar in obese and lean rats. No aortic atherosclerotic lesions were detectable in any group. Collectively, this study shows that a HFHS diet increased myocardial ischemic lesion frequency and abolished the protective effect of female sex on cardiac function. More importantly, the data demonstrates dietary flaxseed protected against the development of small spontaneous cardiac infarcts despite the ingestion of a HFHS diet and the presence of morbid obesity.

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Key Points

Ligation of the coronary artery with a suture in animals induces cardiomyocyte cell death, cardiac contractile dysfunction and arrhythmias. The objectives of the present study were to verify if dietary flaxseed supplementation will alter the incidence of myocardial lesions, blood pressure hemodynamics, atherosclerosis, and cardiac function in JCR:LA- cp rats. The rats will be fed a high-fat, high sucrose diet in the presence or absence of flaxseed to evaluate the effects of both diets on the atherosclerosis and hypertension. The potential for these parameters to exhibit sex differences in their expression was also considered.

First, and most importantly, daily supplementation of the diet with flaxseed exhibited a capacity to reduce the frequency of mini-infarcts in the myocardium. These appeared spontaneously in this animal as small ischemic lesions. The ingestion of a HFHS diet increased the frequency of these myocardial lesions and flaxseed blocked this effect even when both dietary constituents were introduced together. Second, flaxseed was able to protect against cardiac diastolic dysfunction exhibited in obese animals fed a HFHS diet. Third, although there were some minor differences between the responses of the 2 sexes, generally male and female JCR:LA- cp rats responded in a similar fashion to the various interventions employed in this study. Fourth, this animal model did not exhibit hypertension or aortic atherosclerotic lesions despite the presence of elevated circulating cholesterol levels un- der any of the conditions examined in the present study. chemic lesion frequency, reduced cholesterol levels, and improved systolic and diastolic function in the JCR:LA- cp rats. The decrease in ischemic lesions is of particular importance. It is consistent and extends previous findings from our lab that flaxseed can reduce infarct size in a different model of MI. The present results have now extended this cardioprotective effect of dietary flaxseed to a spontaneously occurring MI in the presence of associated morbidities.

By virtue of its effect on decreasing myocardial fibrosis and thus improving IVRT, dietary flaxseed may be considered as an effective strategy against the progression of heart failure with preserved ejection fraction (HFpEF). However, further studies of the underlying mechanisms are also required to generate evidence supporting flaxseed as a highly effective treatment for metabolic syndrome or for preventing the progression to heart failure with preserved ejection fraction. The present study also clearly demonstrates that the JCR:LA- cp rat model of obesity does not manifest atherosclerosis or hypertension, even in the presence of a high fat, high sucrose diet administered over an extended period of time.