title: Alteration of enzyme expressions in mevalonate pathway: possible role for cardiovascular remodeling in spontaneously hypertensive rats.
abstract: BACKGROUND
  The mevalonate pathway is an important metabolic pathway that plays a key role in multiple cellular processes. The aim of this study was to define whether the enzyme expression in mevalonate pathway changes during cardiovascular remodelling in spontaneously hypertensive rats (SHR).
  
  
  RESULTS
  Hearts and thoracic aortas were removed for the study of cardiovascular remodeling in SHR and Wistar-Kyoto rats (WKY). The protein expression of the enzymes in hearts, aortas and livers was analyzed by western blot. The histological measurements showed that the mass and the size of cardiomyocytes, the media thickness and the media cross-sectional area (MCSA) of the thoracic aorta were all increased in SHR since 3 weeks of age. In the heart, there was overexpression of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), and geranylgeranyltransferase type I (GGTase-I), and downregulation of squalene synthetase (SQS) in SHR since 3 weeks of age. In the aorta, besides similar expressions of HMGR, SQS, FDPS and GGTase-I as in the heart, there was upregulation of farnesyltransferase α at 16 and 25 weeks of age and of farnesyltransferase β in 25-weeks-old SHR. Western blot demonstrated overexpression of HMGR and downregulation of SQS in SHR livers at all ages tested.
  
  
  CONCLUSIONS
  The cardiovascular remodeling of SHR preceded the development of hypertension, and altered expression of several key enzymes in the mevalonate pathway may play a potential pathophysiological role in cardiovascular remodeling.
authors.affiliation: Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Han
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Jiang
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Du
authors.forename: Shen-Jiang
authors.initials: SJ
authors.lastname: Hu
mesh_terms: D000367:Age Factors; D000375:Aging; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D015153:Blotting, Western; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000378:metabolism; D051231:Farnesyltranstransferase / Q000378:metabolism; D051228:Geranyltranstransferase / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D008099:Liver / Q000201:enzymology; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020257:Ventricular Remodeling
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006903:Hydroxymethylglutaryl CoA Reductases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051228:Geranyltranstransferase; D013186:Farnesyl-Diphosphate Farnesyltransferase; D051231:Farnesyltranstransferase; D008798:Mevalonic Acid