Monitoring fibrillar collagen turnover in hypertensive heart disease

Time for primary review 32 days. A substantial increase in fibrillar collagen has been observed in the cardiac ventricles of animals 1and humans 2with arterial hypertension. Either reactive or reparative hypertensive myocardial fibrosis is the result of both increased collagen types I and III synthesis by fibroblasts and unchanged or decreased extracellular collagen degradation 3. Hemodynamic and non-hemodynamic factors may be involved in the disequilibrium between collagen synthesis and degradation that occurs in hypertension 4. As shown experimentally 1and clinically 5, 6, a rise in collagen content increases myocardial stiffness and promotes abnormalities of cardiac function. In addition, the perivascular accumulation of collagen fibers may impair the vasodilator capacity of intramyocardial coronary arteries and contribute to the decrease in coronary reserve, which is commonly seen in the hypertensive heart 7. On the other hand, alterations in the electrical activity of the left ventricle in hypertensive patients have been shown to be related to the degree of myocardial fibrosis 6. Although microscopic examination of cardiac biopsies is the most reliable method for documenting and measuring myocardial fibrosis, the development of non-invasive methods to indicate the presence of myocardial fibrosis in hypertensive patients would be useful. We have therefore applied a biochemical method based on the measurement of serum peptides derived from the tissue formation and degradation of fibrillar collagens to monitor the turnover of these molecules in rats with spontaneous hypertension (SHR) and in patients with essential hypertension. ### 2.1 Fibrillar collagen synthesis Fibrillar collagen is synthesized in the fibroblasts as procollagen containing an amino-terminal and a carboxy-terminal propeptide (Fig. 1) 8. After procollagen has been secreted into the extracellular space, the propeptides are removed by specific proteinases, allowing integration of the rigid collagen triple helix into the growing fibril (Fig. 1) 8. Fig. 1 Diagrammatic depiction of … * Corresponding author. Unidad de Fisiopatologiea Vascular, Facultad de Medicina, C/ Irunlarrea s/n, 31080 Pamplona, Spain. Tel.: +34 (48) 425600; fax: +34 (48) 425649.