β2-Microglobulin and TIMP1 Are Linked Together in Cardiorenal Remodeling and Failure

Abstract

Background/Aims: The cardiorenal syndrome is a complication in patients hospitalized with chronic heart failure (CHF). The β₂-microglobulin (b2M) level is an index of decreased glomerular filtration rate (GFR), tissue turnover and inflammation. It is an emerging new predictive marker of cardiovascular events and mortality, but its role as a biomarker of cardiorenal remodeling and failure is still unknown. TIMP1, an endogenous tissue inhibitor of activated matrix metalloproteinases, is a biomarker of heart remodeling and failure. We aimed to evaluate the circulating profile of b2M and TIMP1 in CHF patients, in sedentary controls with no tissue remodeling and in veteran athletes with physiological cardiorenal remodeling and athlete's heart (AH). Methods: We investigated the plasma levels of b2M and TIMP1 in 24 subjects with CHF without primitive renal disease, in 25 sedentary controls and in 30 veteran marathoners with AH over 50 years. Results: The b2M and TIMP1 levels were higher in CHF patients, and there was a correlation between them (r = 0.5287, p < 0.0095). The b2M level correlated with the severity of cardiorenal impairment: with proBNP (r = 0.66, p > 0.0007), percent ejection fraction (r = -0.56, p = 0.0162) and GFR (r = 0.83, p < 0.0001). b2M was also correlated with TIMP1 in AH subjects (r = 0.7548, p < 0.0001) but not in controls. This correlation was independent from GFR in both CHF patients and sedentary controls. Conclusions: In CHF patients, the plasma levels of b2M and TIMP1 were linked together and correlated with the severity of cardiorenal failure. Moreover, a strong correlation between b2M and TIMP1 characterized cardiovascular remodeling not only in CHF patients but also in AH subjects. These findings suggest that clinicians should use b2M and TIMP1 as associated biomarkers of cardiorenal remodeling and failure. © 2014 S. Karger AG, Basel

Single-Cell RNA Sequencing and Quantitative Proteomics Analysis Elucidate Marker Genes and Molecular Mechanisms in Hypoplastic Left Heart Patients With Heart Failure

“…Interestingly, Yokota et al (2020) found that the COL5A1 expression level significantly correlated with scar size after myocardial infarction mechanically, not only in the regulation of the size of cardiac scars but also in tissue mechanical properties in an integrin-dependent manner. The expression level of B2M in the plasma is not simply a significant marker for kidney injury but a novel regulator involved in heart failure and heart remodeling ( Vianello et al, 2015 ). Vianello’s group demonstrated that the B2M level was increased in chronic heart failure patients and that it was positively correlated with the levels of proBNP and GFR but negative in percent ejection fraction ( Vianello et al, 2015 ).…”

“…The expression level of B2M in the plasma is not simply a significant marker for kidney injury but a novel regulator involved in heart failure and heart remodeling ( Vianello et al, 2015 ). Vianello’s group demonstrated that the B2M level was increased in chronic heart failure patients and that it was positively correlated with the levels of proBNP and GFR but negative in percent ejection fraction ( Vianello et al, 2015 ). Using 9,988 participants’ data from the Atherosclerosis Risk in Communities (ARIC) study, we showed a more sensitive advantage in predicting outcomes, including kidney function, cardiovascular disease, and mortality, in the general population for serum B2M levels ( Astor et al, 2012 ).…”

Altered Amino Acid Metabolism in Patients with Cardiorenal Syndrome Type 2: Is It a Problem for Protein and Exercise Prescriptions?

“…Renal biomarkers [ 90 ] including plasma beta 2-microglobulin [ 91 ], N-acetyl-beta-glucosaminidase (NAG) [ 92 ] and urinary kidney injury molecule-1 (KIM-1) [ 93 ] were not available in this study. Thus, a prospective investigation is necessary to address the relationship between levels of kidney injury markers and plasma AA levels.…”

Densification of Type I Collagen Matrices as a Model for Cardiac Fibrosis

“…While Timp1 has been designated as cardiac specific, studies also show profibrotic features of Timp1 in other tissue such as liver, lung, and is a reliable predictor for Dupuytren's disease, a common fibrotic disease that effects finger movements . Its role in cardiac fibrosis, however, might be more significant as it has been linked to overall cardiac remodeling and heart failure . Scleraxis (Scx), in turn, is a transactivator for Col1a2 and other collagen‐associated genes.…”