Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events.
OBJECTIVE
Disturbances of the synthesis and breakdown of the extracellular matrix of arterial walls have emerged as key features of the atherosclerotic process. Altered levels of circulating extracellular matrix markers have frequently been observed in relation to manifestations of atherosclerotic disease and its risk factors.


RESULTS
Research has been focused on the matrix-degrading metalloproteinases, their tissue inhibitors, and procollagen peptides. The most promising matrix metalloproteinase is matrix metalloproteinase-9, which has been observed to predict rapid coronary artery narrowing, ischemic heart disease incidence, abdominal aortic aneurysm expansion, worse outcome in stroke patients, and cardiovascular death. The use of tissue inhibitors of metalloproteinases for prognostication is uncertain thus far. The procollagen marker with most prognostic potential is the marker for type III collagen turnover rate, the N-terminal propeptide PIIINP, higher levels of which predict an adverse outcome after a myocardial infarction and in chronic heart failure, and portend abdominal aortic aneurysm expansion and risk of rupture. Also, the marker for type I collagen synthesis, the C-terminal propeptide PICP, predicts adverse outcomes following myocardial infarction and in chronic heart failure. Extracellular matrix remodeling is also a promising therapeutic target, being favorably affected by several conventional cardiovascular drugs and select dietary interventions. Synthetic matrix metalloproteinase inhibitors are also under development.


CONCLUSIONS
Circulating matrix markers have emerged as candidate biomarkers for predicting risk of subsequent atherosclerotic events. Future large longitudinal observational and intervention studies will determine the role of matrix biomarkers in diagnosis and prognostication, and as targets for intervention in cardiovascular diseases.
Sundström
Johan
J
Department of Medical Sciences and Public Health & Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden. johan.sundstrom@pubcare.uu.se
Vasan
Ramachandran S
RS
D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000097:blood; D001158:Arteries / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D023921:Coronary Stenosis / Q000097:blood; D005109:Extracellular Matrix / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood*; D012307:Risk Factors; D020521:Stroke / Q000097:blood
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D020780:Matrix Metalloproteinase 9