Serum Levels of Hcy, sST2 and CA-125 in CHF Patients and Their Correlation with Cardiac Function Classification.

BACKGROUND: The relationships between serum levels of homocysteine (Hcy), soluble stromelysin 2 (sST2), and tumor-associated cancer antigen 125 (CA-125) and heart failure requires further investigation. The aim of the present study was to evaluate the levels of Hcy, sST2 and CA-125 in patients with congestive heart failure and to correlate these with cardiac function, thereby providing a reference for the clinical diagnosis and treatment of heart failure. METHODS: Seventy patients with chronic heart failure (CHF) diagnosed between August 2020 and July 2022 were classified into heart failure groups II (n = 25), III (n = 23) and IV (n = 22). Seventy individuals with normal physical examination results were selected as the healthy group. Serum Hcy, sST2 and CA-125 levels for all participants were evaluated and correlated with each other and with cardiac function classification. The diagnostic value of individual Hcy, sST2, CA-125 levels for CHF was evaluated, as well as a combination of these factors. RESULTS: Hcy, sST2, and CA-125 levels were lower in the healthy group than in the heart failure group. Moreover, a progressive increase in Hcy, sST2, and CA-125 levels were observed in heart failure groups II, III, and IV. Individual Hcy, sST2 and CA-125 levels, as well as a combination of these factors, were significantly correlated with cardiac function classification (p < 0.05). Hcy, sST2 and CA-125 levels each showed diagnostic value for CHF, with the three combined having the best diagnostic value. CONCLUSIONS: Abnormally high levels of Hcy, sST2 and CA-125 occur in CHF patients and are positively correlated with cardiac function classification. Individual levels of these factors, and particularly a combination of the three, show good sensitivity and specificity for CHF diagnosis that could be widely used in clinical practice.

Matrix metalloproteinase-10 effectively reduces infarct size in experimental stroke by enhancing fibrinolysis via a thrombin-activatable fibrinolysis inhibitor-mediated mechanism.

BACKGROUND: The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown. METHODS AND RESULTS: The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10-null mice (Mmp10(-/-)), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator-induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation-mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in Mmp10(-/-) mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator-treated animals were severely impaired in Mmp10(-/-) mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor-deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect. CONCLUSIONS: A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis.