Alterations in gene expression of series key enzymes in mevalonic acid pathway detected by RNA array in spontaneously hypertensive rats

AIM: To explore the alteration in gene expressions of several enzymes in mevalonic-acid (MVA) pathway in SHR.METHODS: 294 samples of total RNA were extrated from the tissues of ventriculum, aortic smooth muscle, liver and kidney in SHR and WKY. RNA array was used to determine the mRNA level of several enzymes in mevalonic acid pathway.RESULTS: (1) Systolic blood pressure of SHR surpassed that in WKY since the 6th week (P<0.01). (2) The level of cholesterol in serum was significantly lower in SHR than that in WKY (P<0.01), while that in tissue between two bands had no difference. (3) The gene overexpressions of four enzymes in the four tissues of SHR (P<0.01), including farnesyl diphosphate synthase (FDS), isopentenyl diphosphate isomerase (IDI), farnesyltransferase alpha subunit (FT1), farnesyltransferase beta subunit (FT2), which catalyze the vital mid-productions in MVA pathway, were observed. (4) Gene overexpressions of some enzymes assayed in MVA pathway in SHR renal tissue were observed since 4th week (P<0.01), including 3-hydroxy-3-methylglutaryl -coenzyme A reductase (HMGR), mevalonate kinase (MVK), mevalonate decarboxylase (MVD), squalene synthetase (SQS) and squalene epoxidase (SQ). (5) The gene expressions of these enzymes in ventriculum, aortic smooth muscle and liver showed no difference between two band rats, eg HMGR, MVK, MVD, SQS, SQ.CONCLUSION: The gene expressions of several enzymes in mevalonic acid non-cholesterol pathway in SHR ascend and the mechanism will be further explored.