Extrahepatic Vitamin K-Dependent Gla-Proteins-Potential Cardiometabolic Biomarkers.

One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.

HER2-Targeted Therapy-From Pathophysiology to Clinical Manifestation: A Narrative Review.

Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation.

Galectin-3 in patients with atrial fibrillation and restored sinus rhythm.

INTRODUCTION: Cardiac fibrosis is the hallmark of atrial remodeling in atrial fibrillation. Galectin-3 (Gal-3) is a biomarker of fibrosis. It is well studied in heart failure, but the data about its role in atrial fibrillation are sparse. AIM: The aim of the study was to evaluate the levels of Gal-3 in patients with atrial fibrillation after sinus rhythm restoration, to examine the association between this biomarker and other factors for developing atrial fibrillation and to assess its prognostic role. MATERIALS AND METHODS: We included 67 patients (35 male) at the mean age of 67.36±7.25 years, with Gal-3 test after sinus rhythm restoration, a subgroup of participants in placebo-controlled randomized clinical trial of treatment with spironolactone. They were followed up for atrial fibrillation recurrence and hospitalizations. The effect of demographic parameters and other factors on Gal-3 levels were evaluated before and one year after treatment. RESULTS: Mean Gal-3 at baseline was 16.9±6.8 ng/ml. Higher levels of Gal-3 were associated with female gender (р=0.008), increasing age (р=0.005), renal dysfunction (p<0.0001) and gout (р=0.002). Higher thromboembolic risk as assessed by CHA2DS2-VASc score was significantly related to Gal-3. The levels of biomarker did not affect the number of atrial fibrillation recurrences (p=0.9) and hospitalizations. No correlation was found with treatment with spironolactone, antiarrhythmic and antihypertensive drugs. CONCLUSIONS: Higher Gal-3 in atrial fibrillation was associated with female sex, renal dysfunction, and history of gout. The levels of Gal-3 were not related to rhythm control. Treatment with spironolactone did not affect the biomarker of fibrosis Gal-3 in AF patients. Higher Gal-3 was related to high embolic risk.