Effects Of Fluvastatin On The Endothelial Function In Patients With Acute Myocardial Infarction

PrefaceAcute myocardial infarction ( AMI) is a serious disease that threatens human health, with the beginning of endothelial dysfunction . Following the dysfunction are the impairment of endothelial - dependent vasodilatation, elaboration of anti - adhesion, anticoagulation, and anti - proliferation of smooth muscle. Endothelial dysfunction plays an important role in acute coronary syndrome ( ACS) as well as plays a predictor in early AMI. Present studies designed to investigate endothelial injury and dysfunction are getting much more attention.In recent years , fluvastatin , as a lipid - lowering drug , is wildly used for the therapy of AMI. Previous studies have shown that fluvastatin can reduce mortality of ACS by promoting endothelial function as well as stabilize atherosclerotic plaque. However few studies focus on circulating endothelial cell (CEC) , which are from the lesion of endothelium.The purpose of this study was to discuss the effects of fluvastatin on the endothelial function in patients with AMI by observing CEC and evaluating endothelial - dependent diastolic - systolic function . CEC is a directed and specified mark in living tissue and the results were more accurate than before .Materials and methodsCEC were tested by flow cytometer in 30 Patients with AMI and in 30 age -matched normal subjects and the endothelial - dependent vasodilatation ( EDD) of brachial artery and non - endothelial - dependent vasodilatation ( NEDD) were measured by ultrasound technique in these patients. The patients with AMI re-ceived conventional medication ( ACEI, β - blocker, Asprin ) plus fluvastatin 40 mg/d for 4 weeks. The studies of CEC and vasodilatation of brachial artery for each patient were performed before ,4 weeks after treatment. CEC were tested by flow cytometer, EDD and NEDD tested by ultrasound technique, blood lipid tested by enzyme method. All the results were scanned and semi - quantitated by computer. SPSS 10. 0 software was used to examine all values.Results1. In patients with AMI, the number of CEC in the patients( 1030 ±150)/ ml was greatly increased compared with the contrasts(359 ±65 ) /ml, P <0. 01.2. EDD(3. 34 ± 1. 79 ) % was significantly reduced compared with that in the age - matched normal subjects (7.95 ± 2. 93 ) % , P < 0.01, NEDD (9. 92 ± 5.31)% was also reduced compared with that in the age - matched subjects.3. The number of CEC in the patients was significantly reduced after therapy (849±163)/ml, P<0.01.4. EDD was significantly improved after 40 mg/d fluvastatin plus conventional therapy (5. 23 ± 2. 06 ) % , P < 0. 01, but NEDD ( 9. 12 ± 4. 56 ) was no change after therapy, P > 0. 05.5. Total cholesterol ( TC) , triglyceride ( TG) , low - density lipoprotein cholesterol ( LDL - C) were significantly decreased after therapy , P <0. 05.DiscussionThe surface of the inner lumen of vascular is covered with endothelial cells with the function of maintaining of permeability barrier , keeping normal blood flow and material exchange of vascular. Vascular endothelial cells are the biggest endocrine organ by releasing more than tens of biological substances through autocrine and paracrine and play an important role on vascular homeostasis ,on the other hand ,they are the target organ of biological substances. The endothelium also plays a vital role in vascular regulation, thrombosis and thrombolysis balance , vascular smooth muscle cell proliferation, trans - endothelial leukocytemigration, collagan and poly glycoprotein synthesis. The onset of athrosclerosis is the dysfunction of endothelium, which can be defined as the partial or complete loss of balance between vasoconstrictors and vasodilators, growth promoting and inhibiting factors, pro - antherogenic and anti - antherogenic factors, and pro -coagulant and anti - coagulant factors. Previous studies approved that endothelial dysfunction are related positively to the degree of lesion and activation . It appears that the dysfunction is far earlier than the formation of atherosclerotic plaques in coronary heart disease ( CHD). Impaired vascular can produce cytokines which can lead endothelium dysfunction thus promoting atheroscleosis. Hypercholesterolemia can be the excuses of disorders of vascular hemeostasis , It can reduce the biological activity of nitric oxide ( NO) , increase endothelium immunity and oxidization .promote adhesion molecules and decrease endothelial- dependent vasodilatation . it is reported that cholesterol can lead dysfunction of endothelium and is related to the degree of oxidized - LDL { OX - LDL). OX- LDL contains function of cytotoxicity to various cells and chemotasis to monocytes , plus inhibiting endothelium dilatation and affecting the activity of tranver-sion factors.Many famous clinical trials (4S , CARE, LIPID) supported that statins can reduce the mortality incidence of ACS in the first and second prevention process. This may be related to the foilowings 1. Promoting endothelium function :by elevating the concentration of NO. 2. Reduce the formation of atheroscleotic plaque cell: by inhibiting the proliferation of smooth muscle cells and macrophages 3. Alleviate the inflammation of plaque and elaborate antithrombotic molecules.In lipid - lowering therapy blood reduction of cholesterol is positively to the endothelial - dependent vasodilatation . It is known that lipid dysfunction is important in acute phase of AMI. CEC is the only direct specified predictor of living tissue in the lesion of endothelium. The method of Takahashi is effective but with disadvantages of the following : large amount blood sample taking, platelet no removing, number subjectively counting . Our study will focus on CEC counting by flow cytometer with small amount of blood sample(2.4ml). The eccentric blood sample will be adequate of CEC cell layer with separating of CEC.