INCREASED CYCLIN-DEPENDENT KINASE IN AORTIC TISSUE OF RATS FED HOMOCYSTEINE

Background. Hyperhomocyst(e)inemia is strongly associated with occlusi ve arterial disease. Several mechanisms for the development of vascula r lesions have been described. A direct effect of homocysteine on prol iferation of smooth muscle cells and collagen expression was proposed recently. These observations led us to examine the effect of homocyste ine on cyclin dependent kinase, the starter of mitosis and reflecting proliferation, Methods and results. Thirty Him:OFA rats were divided i nto three groups, Ten animals were fed for a period of six weeks 50 mg /kg body wt per day homocysteine, ten the same dose of homocysteic aci d and ten remained untreated controls. At the end of the experiment we determined aortic cyclin dependent kinase, phosphokinases A and C, ao rtic homocyst(e)ine and aortic hydroxyproline. Aortic cyclin dependent kinase was significantly (p = 0.0001) elevated in the homocysteine tr eated group (mean 120 +/- 15) compared with the homocysteic acid treat ed group (mean 71 +/- 11) or the untreated group (mean 72 +/- 10 fmol/ mg aortic tissue). Aortic homocyst(e)ine was significantly higher in h omocysteine treated animals (p = 0.0002) strongly correlating with cyc lin dependent kinase (r squared = 0.85, p = 0.0001) and with aortic hy droxyproline (r squared = 0.66, p = 0.0001), which in turn was signifi cantly (p = 0.0001) increased in the homocysteine treated group. Phosp hokinases A and C determined to rule out nonspecific effects on kinase s were not increased by administered homocysteine. Conclusions. Our fi ndings indicate that homocysteine stimulates aortic cyclin dependent k inase with the possible consequence of proliferation of aortic cells. Aortic collagen accumulation could be explained by either the homocyst eine-effect on collagen synthesis described in literature, or secondar ily, by increased proliferation of collagen producing aortic cells.