The Effects Of Hyperlipidemia On The Expression Of Connexin37, 40, 43, 45 Messenger RNA Of Aortal Walls And Endothelial Function

Atherosclerosis is a multifactorial disease process initiated by a variety of pathogenetic mechanisms. Initiation and progression of the atherosclerotic plaque involve complex patterns of interaction between the cells of the arterial wall. In which hypercholesterolemia is the crucial factor and endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. More recently, another form of cell-to-cell interactive communication via gap junction and the component proteins of gap junction, connexins, have been drawing more and more attention. Based on the atherosclerosis mode of rat, we sought to (1) clarify the response of endothelial function and connexins of aortal walls to hyperlipidemia and atherosclerosis; (2) find out the relationship between the expression of connexins and the endothelial function; (3) study the link between the atherosclerosis and both the expression of connexins as well as the endothelial function.Methods Adult (8 weeks old), male, Wistar rats were subjected to the following regimens respectively: (1) normal chow +saline (ip) for 8 or 22 weeks (group C); (2) Propylthiouracil and cholic acid chow + VitD3(ip) for or 22 weeks(group PV); (3) compound hyperlipide chow + VitD3 (ip) for 8 or 22 weeks(group HF);(4) Poloxamer-407(ip, 0.5g/kg, every 3rd day) + VitD3 (ip) for 8 or 22 weeks(group P). Techniques , such as RT-PCR, immunohistochemistry, ect, were been used. The levers of CH, TG, apo-Al, apo-B, Ca2+, NO, NOS, O2- and SOD of serum were assessed. The gene and protein expression profiles of Cx37, Cx40, Cx43 and Cx45 of aortic walls were analyses. The lesions of aortic walls caused by hypercholesterolemia were examined.Results The serum levers of Ca2+ were markedly increased in the rats of group PV, HF and P, which were treated VitD3(ip), compared with the group C. The bodyweight was apparently decreased in the rats of groups PV and HF.In the group HF, the concentration of serum CH 5-fold increased compared with that of the group C and base line. The concentration of serum TG also 4~5-fold increased compared with that of the group C and base line. The content of apo-Al decreased and content of apo-B increased. At the 8th weeks of study, compared with group C, the lever of serum NO, iNOS and O2 " was obviously higher, where the lever of serum SOD was significantly lower, the lever of eNOS demonstrated no significant difference. At the 22th weeks of study, the serum lever of NO> eNOS, O2 ' was still higher then that of group C, the SOD showed no significant difference. At the 8th weeks of study, the SMC and EC of aortic walls of rats showed proliferation. The label of Cx43 of aortic and the expression of Cx43 mRNA of the abdominal aortas was up-regulation. The expression of Cx37, Cx40, and Cx45 mRNA of the abdominal aortas was no difference compared with group C. The aortas of rat of this group formed typical atherosclerosis lesion.In the group P, the concentration of serum CH 2-fold increased compared with that of the group C and base line. The concentration of serum TG 15~20-fold increased compared with that of the group C and base line. The content of apo-Al decreased and content of apo-B increased. At the 8th weeks of study, compared with group C, the lever of serum NO, iNOS, eNOS and O2~" was no significant difference, where the serum SOD was significantly lower. At the 22 * weeks of study, the serum eNOS was higher then that of group C, the others showed no significant difference. The expression of Cx37, Cx40, Cx43, Cx45 mRNA of the abdominal aortas was no difference compared with group C. No any atherosclerosis lesion of the aortas of these rats was observed.In the group PV, compared with group C, the lever of serum CH, TG, apo-Al,apo-B, iNOS, eNOS, O2 ", SOD was no significant difference, where the lever of serum NO was significantly higher at 22th week. The expression of Cx37, Cx40, Cx43, and Cx45 mRNA of the abdominal aortas was no difference compared with group C.Compared with 8 week, the expression of Cx37, Cx40, and Cx43 mRNA of the abdominal aortas of all rats was significantly downregulation (P<0.05) . The expression of Cx45 mRNA showed upregulation (P>0.05) .There were positive correlation between the serum CH content and the serum NO (r=0.69, P=0.00) , iNOS (i=0.72, P=0.00) , R O2~- (r=0.73, />=0.00) . The age showed a negative correlation with the expression lever of Cx37 mRNA(r=-0.51, /M).00), Cx40 mRNA(r=-0.35, P=0.00), Cx43 mRNA(r=-0.80, P=0.00) as well as a positive correlation with expression lever of Cx45 mRNA(r=0.27, P=0.02). There was no correlation between Cx and serum CH, TG, apo-A|, apo-B, NO, iNOS, eNOS, O2~and SODConclusions(1) Under these circumstances the chronic hypercholesterolemia damaged the endothelial function and upregulated the expression of Cx43 gene and protein of the aortic wall as well as induced formation of typical atherosclerosis lesions. The chronic hypertriglyceridemia was not the important factors of atherogenesis, although it caused endothelial dysfunction to some extent.(2) The hypercholesterolemia caused hyperexpression of Cx43, this condition promoted to form the atherosclerosis lesions; The mRNA lever of Cx37, Cx40, Cx45 of the rat abdominal aortas was free of the affection of the hypercholesterolemia and hypertriglyceridemia.