Enhancement of the coagulation system in spontaneously hypertensive and hyperlipidemic rats.
As a risk factor for cardiovascular and cerebrovascular disease, hypertension and hyperlipidemia are believed to provoke vascular damage leading to a hypercoagulative state. The aim of the present study was to investigate the coagulative and fibrinolytic activity and hepatic mRNA expression of the coagulative factors in spontaneously hypertensive and hyperlipidemic female rats (SHHR:>150 mmHg of systolic blood pressure, >150 mg/dl of plasma cholesterol). Plasma levels of fibrinogen, thrombin-antithrombin III (ATIII) complexes and ATIII in the SHHR at 9 months of age increased significantly compared with those of age-matched Sprague-Dawley rats (SD). In the SHHR, the hepatic mRNA expression of the alpha- and beta-chains, but not the gamma-chain of fibrinogen and prothrombin was significantly enhanced. Therefore, the hyperfibrinogenemia in the SHHR was demonstrated to be due to the increase in hepatic mRNA expression of alpha- and beta-chains of fibrinogen. The pathological findings of the aortic arch from the 9-month old SHHR were cytoplasmic vacuolization and intimal thickening in the endothelium. These results suggest that hypercoagulation concomitant with the increase in hepatic mRNA expression of fibrinogen components may contribute to the development of atherosclerosis in the SHHR.
Amagasa
Hidetoshi
H
Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.
Okazaki
Masako
M
Iwai
Shinichi
S
Kumai
Toshio
T
Kobayashi
Shinichi
S
Oguchi
Katsuji
K
D000818:Animals; D000990:Antithrombin III; D001779:Blood Coagulation Factors / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D006949:Hyperlipidemias / Q000097:blood*; D006973:Hypertension / Q000097:blood*; D008099:Liver / Q000378:metabolism; D010447:Peptide Hydrolases / Q000097:blood; D010958:Plasminogen / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D001779:Blood Coagulation Factors; D012333:RNA, Messenger; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D010958:Plasminogen; D010447:Peptide Hydrolases