Circulating Biomarkers of Collagen Metabolism in Cardiac Diseases

Abstract

A lterations of the structure and composition of cardiomyocyte and noncardiomyocyte compartments of the myocardium appear to play a central role in the pathogenesis of heart failure (HF) associated with a number of cardiac diseases. Among these alterations, changes in the quantity and quality of the extracellular matrix, including the collagen network, have been characterized that induce remodeling of the myocardium and ultimately deteriorate left ventricular (LV) function and facilitate the development of HF. Studies on circulating biomarkers of collagen metabolism have attracted the attention of the medical community, and some circulating biomarkers have been proposed as potential useful tools to improve diagnosis, prognosis, and therapy in cardiac diseases that develop HF. 1 However, the available data are far from conclusive and from affording incremental value to the knowledge provided by more classic diagnostic tools. This is due mainly to 3 limitations. First, collagen is the most abundant protein in the body, and its turnover is so dynamic that not all circulating molecules proposed as biomarkers actually reflect changes in collagen metabolism, namely at the cardiac level. Second, a thorough understanding of the association of a given biomarker with the pathological features of the collagen network in the cardiac disease under study has not been considered essential, thus weakening its pathophysiological meaning. Third, several methodological issues may introduce a number of confounding factors into the measurements of circulating biomarkers of collagen metabolism, thus bringing into question the validity of the available results. Therefore, this article is not aimed at providing a systematic review of all the published information on circulating biomarkers of collagen metabolism in cardiac diseases but at analyzing the biochemical, pathophysiological, and methodological aspects to be taken into account to overcome the above limitations and to improve the clinical applicability of such molecules. Circulating Biomarkers of Collagen Metabolism Collagen MetabolismThe extracellular matrix contains a fibrillar collagen network, a basement membrane, proteoglycans and glycosaminoglycans, and bioactive signaling molecules. The collagen network is a metabolically active structure in the sense that the balance between the synthesis and degradation of collagen determines its turnover, which is estimated to be from 80 to 120 days. 2 The turnover is regulated by fibroblasts and by fibroblasts differentiated to myofibroblasts (Figure 1). 3 These cells respond to mechanical stretch, autocrine and paracrine factors generated locally (eg, vasoactive peptides such as angiotensin II and growth factors such as transforming growth factor-␤ or connective tissue growth factor), and hormones derived from the circulation (eg, aldosterone). In addition, a number of proinflammatory cytokines (eg, tumor necrosis factor-␣, interleukin-1 and -6) secreted by monocytes and macrophages also influence the function of fibroblasts and my...

Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction

“…Extracellular matrix alterations, which contain synthesis and degradation of collagen, occur not only in the myocardium but also in the arterial wall, kidneys, lungs, and liver in systemic disease (e.g. HF and chronic liver disease) 29, 30. Collagen‐dependent ventricular stiffness is increased in HFpEF 1, 2, 3, 4, 5.…”

From aldosteronism to oxidative stress: the role of excessive intracellular calcium accumulation

“…Depending on its site and magnitude, collagen fiber crosslinking and relative abundance of type I and III collagens will determine the stiffness and where type 1 collagen fibers resemble the tensile strength of steel. 21 Fibrosis can adversely increase myocardial stiffness leading to diastolic heart failure, or as more recently coined heart failure with preserved ejection fraction (reviewed in Zile and Brutsaert 22,23 and Díez 24 ). Diastolic heart failure is commonly seen with the concentric hypertrophy that accompanies arterial hypertension.…”

Blood Level of Collagen Biomarkers and Sulfated Glycosaminoglycans in Acute Transmural Myocardial Infarction

“…В миокарде соединительная ткань представлена внеклеточным матриксом -коллагеновой сетью, связывающей кардиомиоциты, фибробласты, сосуды и нервы [4,7]. Большая часть коллагеновых волокон внеклеточного матрикса миокарда представлена кол-лагеном I и III типов [7].…”

“…Большая часть коллагеновых волокон внеклеточного матрикса миокарда представлена кол-лагеном I и III типов [7].…”

“…Все циркулирующие биомаркеры метаболизма коллагена можно разделить на 2 группы: биомар-керы, связанные с синтезом молекул коллагена и свя-занные с его деградацией [7]. К первым относится карбокситераминальный пропептид проколлагена I типа (PICP), а ко вторым -карбокситерминальный телопептид коллагена I типа (CITP).…”