Relationship Between Ethanol And Coronary Collateral Circulation After Acute Myocardial Infarction In Rats And Intervention Study

Background and ObjectiveCurrently,cardiovascular disease is the leading cause of deaths in the world. There are many risk factors associated with coronary heart disease(CHD),such as family history,age,hypertension,high cholesterol, obesity,and harmful use of alcohol and so on.Alcohol as a risk factor for CHD which can be changed. Substantial epidemiological evidence links moderate alcohol consumption with a lower risk of CHD.These evidence includes results from geographic comparisons, large cohort studies.U or J-shaped relationship between moderate alcohol consumption and the morbidity, mortality of CHD.Heavy drinking was associated with degree of coronary calcification,which increases the morbidity and mortality of CHD.Most vitro studies have shown that consumption of small amounts of alcohol can increase the expression of VEGF,which can promote angiogenesis.Long-term clinical studies in patients with coronary heart disease have found that consumption of small amounts of alcohol have better coronary collateral circulation than non-drinker or alcoholism.But the mechanism of different alcohol consumption on angiogenesis after acute myocardial infarction is unclear.Hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) has been the cornerstone of primary and secondary prevention of coronary heart disease.Clinical evidence has been demonstrated that long-term administration of statin therapy significantly reduces the risk of cardiovascular events.The patients with long-term use of statins will significantly benefit from the mechanism of reduce LDL-C,anti-inflammatory, antioxidant, protecting vascular endothelial cells.The latest study also found that statins can inhibit ventricular remodeling, and contribute to the cardioprotective effects of ischemic myocardial angiogenesis.Therefore,we hypothesized that heavy-drinking can inhibit angiogenesis after myocardial infarction in ischemic myocardium,but whether use of statins can able to reverse this inhibition of angiogenesis? There is no relevant reports.In this study,firstly, we use the animal model of acute myocardial infarction observed different amounts of alcohol intake affect on expression of vascular growth regulators (including VEGF and endostatin) in ischemic myocardial.Secondly,if the hypothesis is true,we will further see whether statins can reverse the inhibition of heavy-drinking on angiogenesis in order to provide the theoretical basis for the search for new interventions.Part Ⅰ Effect of ethanol on the coronary collateral circulation after acute myocardial infarction in ratsMethodsSprague Dawley(SD) male rats were randomly divided into four groupsrsham group,water-control group(distilled water5g·kg-1·d-1) and ethanol groups:low dose group(50%ethanol,0.5g·kg-1·d-1),and high dose group(50%ethanol,5g·kg-1·d-1).After treatment for4weeks, all animals were made into the model of myocardial infarction and sacrificed after3days.The microvascular density(MVD) were observed by immunohistochemical SP method. The levels of VEGF and endostatin in the ischemia myocardium were measured by ELISA.ResultsCompared with sham group, MVD,the expression of VEGF and endostatin were significantly increased in water-control group(318.7±18.6vs217.4±26.5;306.9±53.9vs194.1±11.3;88.7±3.4vs70.6±6.3,P<0.05).In low-dose group, MVD and the level of VEGF were significantly higher than water-control group(128.6±12.9vs88.7±3.4;438.2±46.2vs318.7±18.6,P<0.05), but the level of endostatin were significantly reduced (230.7±48.1vs306.9±53.9,P<0.05).While in the high dose group,MVD were significantly reduced (55.4±8.6vs88.7±3.4,P<0.05), the level of VEGF had no significant difference with the control group,but endostatin was significantly increased (437.5±66.7vs306.9±53.9,P<0.05).Part II Rosuvastatin reverses the inhibition of heavy drinking on angiogenesis after acute myocardial infarction in ratsMethodsSD male rats were randomly divided into3groups:rosuvastatin pretreated group[rosuvastatin[(20mg-kg-1·d-1+50%ethanol(5g-kg-1·d-1)],water-control group and heavy-drinking group as the first portion.From4weeks pre-operation,rosuvastatin pretreated group was performed by gavage administration with ethanol and rosuvastatin.Myocardial infarction models were established after4weeks.Rats were sacrificed on the3rd day after acute myocardial infarction.The microvascular density(MVD) were observed by immunohistochemical SP method.ELISA was adopt to test VEGF and endostatin expression levels in the ischemia myocardium tissue.ResultsCompared to heavy-drinking group.MVD in rosuvastatin pretreated group were significantly increased compared to heavy-drinking group(73.1±3.2vs55.4±8.6,P<0.05),but the levels of VEGF and endostatin were no significant difference among two groups.Conclusions1.Ethanol can change the expression of VEGF and endostatin after acute myocardial infarction.2.Low-dose of ethanol can promote coronary angiogenesis by increasing the expression of VEGF.3.Heavy-drinking could inhabit angiogenesis by increasing the expression of endostatin after myocardial infarction.4.Rosuvastatin can reverse the inhibition of heavy-drinking on angiogenesis without induction of VEGF and endostatin.