Background-This study was designed to investigate whether collagen type I degradation is altered in patients with essential hypertension and whether this alteration could be related to disturbances in the serum matrix metalloproteinase pathway of collagen degradation. A second aim of the study was to assess whether some relation exists between serum markers of collagen type I degradation and left ventricular hypertrophy in hypertensive patients. Methods and Results-We measured serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP) as a marker of extracellular collagen type I degradation, of total matrix metalloproteinase-1 (MMP-1), or collagenase, of total tissue inhibitor of metalloproteinases 1 (TIMP-1), and of MMP-1/TIMP-1 complex in 37 patients with never-treated essential hypertension and in 23 normotensive control subjects.

These findings suggest that tissue synthesis of collagen type III and type I is abnormally increased in essential hypertension and can be normalized by treatment with lisinopril. On the other hand, our results suggest that serum PIIIP and PIP are related to several anatomic and functional alterations of the hypertensive left ventricle. Serum procollagen peptide measurements may therefore provide indirect diagnostic information on the myocardial fibrosis associated with arterial hypertension.

Procollagen type III amino-terminal peptide (PIIIP) is cleaved off procollagen type III during the biosynthesis of type III collagen. Thus, to assess the synthesis of collagen type III in essential hypertension, we determined the serum concentrations of PIIIP in 24 patients with never-treated essential hypertension and in 30 normotensive controls. In addition, serum concentrations of PIIIP were measured in 15 patients after receiving lisinopril during 6 months. Serum PIIIP was higher in hypertensives than controls (11.20 +/- 0.76 v 8.47 +/- 0.77 ng/mL, mean +/- SEM, P < .01). A direct correlation was found between serum PIIIP and plasma renin activity (r = 0.54, P < .01) in the group of hypertensives. In addition, serum PIIIP was correlated inversely with maximal early transmitral flow velocity measured during diastole by Doppler echocardiography (r = -0.74, P < .001) in the group of hypertensive patients. The serum PIIIP levels decreased significantly in patients treated with lisinopril (11.76 +/- 0.84 v 8.47 +/- 0.66 ng/mL, P < .01). A significant increase of plasma renin activity and a significant decrease of plasma aldosterone was observed in these patients after treatment with lisinopril. These results suggest that increased collagen type III synthesis is present in patients with essential hypertension. Abnormal synthesis of collagen type III in essential hypertension may be related to the activity of circulating renin-angiotensin-aldosterone system. Whether an excessive synthesis of myocardial collagen type III is responsible for increased serum PIIIP present in essential hypertension deserves further investigation.

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