Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study

Abstract

Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.

Prognostic value of 12 novel cardiological biomarkers in stable coronary artery disease. A 10-year follow-up of the placebo group of the Copenhagen CLARICOR trial

“…Biomarkers included as newer biomarkers were YKL40/µg/L 8 ; hs-cTnT/ng/L 9 ; binary pregnancy associated plasma protein-A (binary-PAPP-A), which is coded as 1 if PAPP-A was ≥4 mIU/L or 0 otherwise 10 ; pro-BNP/ng/L 9 ; cathepsin-B/µg/L 6 18 ; endostatin/ng/mL 19 ; cathepsin-S/µg/L 6 20 ; sTNFR1/pg/mL and sTNFR2/pg/mL 5 21 ; NGAL/ng/L 22 ; calprotectin/mg/L 11 and OPG/ng/L. 12 Due to storage problems some marker data are missing on some patients.…”

“…Briefly, the biomarkers are (1) serum N-terminal pro-B-type natriuretic peptide (pro-BNP), a marker of left ventricular dysfunction and heart failure; (2) high-sensitive assay cardiac troponin T (hs-cTnT) indicating myocardial ischaemia; (3) YKL40 found to be predictive of acute myocardial infarction (AMI), CV death and non-CV death; (4) the glycoprotein osteoprotegerin (OPG), which is positively related to coronary calcification, Open access vascular stiffness and the presence of unstable atherosclerotic plaques; (5) pregnancy-associated plasma protein A (PAPP-A), a marker of vulnerable plaques in coronary arteries; (6) cathepsin-B and (7) cathepsin-S, a group of proteinases that have been suggested to be causally involved in the different stages of the atherosclerotic process; (8) endostatin, an endogenous angiogenesis inhibitor suggested to mirror an increased neovascularisation induced by vascular or myocardial ischaemia; the soluble receptors, (9) soluble tumour necrosis factor receptor 1 (sTNFR1) and (10) soluble TNF receptor 2 (sTNFR2), suggested to portray information about a systemic inflammatory state that is independent of other more established inflammatory markers; (11) calprotectin and (12) neutrophil gelatinase-associated lipocalin (NGAL), both released from neutrophils when the cells are activated. Circulating levels of neutrophils and their activation products have been shown to be markers for plaque instability in both primary and secondary prevention of CV diseases.…”

“…Our group has tested the individual importance of many of these biomarkers, and in many studies statistical inference supports the view that biomarkers may improve the prediction. [5][6][7][8][9][10][11][12] Our objectives were to clarify: (1) which of these newer biomarkers maintain their prognostic importance if all of them were simultaneously available and were combined with the routinely available clinical and laboratory information, and (2) what would then be their relative practical contribution if they were added to the 'standard predictors' such as age, smoking, plasma lipids, etc. In accordance with our published statistical analysis plan, 2 our analysis focusses on all-cause death and on a composite outcome comprising AMI, unstable angina pectoris (UAP), cerebrovascular disease (CeVD) and death.…”

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

“…Indeed, cardiac disease has been described in MPS III patients as well as in patients affected by the other MPS subtypes [178,179]. Multiple evidence demonstrated the involvement of CTSs in many cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, myocardial infarction, and hypertension, some of which are common clinical manifestations in MPSs [8,10,[17][18][19]36,56,61,66,76,80,81]. In particular, CTSB results in being up-regulated in cardiomyocytes in response to hypertrophic stimuli both in vivo and in vitro [180].…”

“…In particular, CTSB results in being up-regulated in cardiomyocytes in response to hypertrophic stimuli both in vivo and in vitro [180]. Furthermore, CTSB was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease [18]. A specific CTSB inhibitor, namely CA-074Me, reduced cardiac dysfunction, remodeling, and fibrosis in a rat model of myocardial infarction [181].…”