Cross-sectional relations of multiple biomarkers representing distinct biological pathways to plasma markers of collagen metabolism in the community
- 1 June 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal Of Hypertension
- Vol. 27 (6), 1317-1324
- https://doi.org/10.1097/hjh.0b013e328329fc20
Abstract
Objective Hyperhomocysteinemia, neurohormonal activation, inflammation and altered fibrinolysis have been linked to atherothrombosis as well as to myocardial fibrosis and heart failure. Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample. Methods We related nine biomarkers representing select biologic pathways (independent variables: C-reactive protein, B-type natriuretic peptide, N-terminal proatrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and homocysteine) to three plasma markers of collagen turnover [dependent variables, separate models for each: aminoterminal propeptide of type III collagen, tissue inhibitor of metalloproteinases-1 and matrix metalloproteinase-9 (present versus absent)] in 921 Framingham Heart study participants (mean age 57 years; 58% women). Participants were separated a priori into those with left ventricular end-diastolic dimensions and wall thickness below sex-specific median values (referent group) and either measure at least 90th sex-specific percentile (‘remodeled’ group). We used stepwise multivariable regression analysis adjusting for cardiovascular risk factors to relate the panel of systemic biomarkers to the three biomarkers of collagen metabolism. Results Plasma homocysteine was positively related to all three markers of collagen metabolism in the remodeled group and to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in the referent group. Plasminogen activator inhibitor-1 was positively related to aminoterminal propeptide of type III collagen and tissue inhibitor of metalloproteinases-1 in both groups, whereas the natriuretic peptides were associated positively with these collagen markers in the referent group. Conclusion In our large community-based sample, plasma homocysteine and plasminogen activator inhibitor-1 were positively related to circulating collagen biomarkers, consistent with experimental studies implicating these pathways in cardiovascular collagen turnover.Keywords
This publication has 34 references indexed in Scilit:
- Overexpression of Urokinase by Macrophages or Deficiency of Plasminogen Activator Inhibitor Type 1 Causes Cardiac Fibrosis in MiceCirculation Research, 2004
- Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart studyEuropean Heart Journal, 2004
- Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures - The Framingham Heart StudyCell Metabolism, 2004
- Relations of Serum Aldosterone to Cardiac StructureHypertension, 2004
- Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarctionJournal of Applied Physiology, 2004
- Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart StudyEuropean Heart Journal, 2004
- Effect of experimental hyperhomocysteinemia on cardiac structure and function in the rat.2004
- Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bedAtherosclerosis, 2003
- Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive ratsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2003
- Plasma Homocysteine and Risk for Congestive Heart Failure in Adults Without Prior Myocardial InfarctionJAMA, 2003