Hypoxia is involved in severe cardiac conditions such as heart failure and myocardial infarction. Therefore, understanding the molecular mechanisms underlying hypoxia is crucial for developing effective therapeutic strategies. Specifically, one in vitro hypoxia model involves reducing oxygen concentration, thereby emulating many features observed in cardiac ischemia in rodents and patients. One way to overcome the infrastructure challenges in basic research laboratories (e.g., anaerobic chamber) is to use chemically-induced hypoxia models. Cobalt chloride (CoCl2) treatment provides an inexpensive, accessible, and highly reproducible model in diverse cell types, as it mimics many of the cellular processes activated during hypoxia/ischemia. Paradoxically, no compendium addresses these processes beyond oxidative stress, let alone focusing on cardiac tissue. Hence, our objective was to describe how other processes, such as mitochondrial dysfunction, calcium handling, apoptosis, autophagy, inflammation, and endoplasmic reticulum stress, interact negatively in cardiac cells exposed to CoCl2 and to examine their cardiomyocyte-level toxicological effects.
Previous studies suggest that HDLs may protect against the effects of acute injury. Given their multiple beneficial properties, this study aimed to investigate whether exogenous HDLs administration reduces acute tissue damage in a HgCl2-induced renal injury model, potentially contributing to health improvement and disease prevention. Acute tubular injury was induced in male Wistar rats with a single intraperitoneal dose of 3.5 mg/kg HgCl2 (ATI group). Two additional groups received either HDLs (ATI + HDL group) or apolipoprotein B-containing lipoproteins (ATI + Lp-B) isolated from human plasma, at a dose equivalent to 0.9 mg of cholesterol per 100 g of body weight, administered twice on consecutive days. The study follow-up lasted four days. Urine and blood samples were collected to evaluate renal function markers. Histological analysis was also performed. In vitro, the ability of these lipoproteins to maintain cell viability under mercury exposure was assessed using the HEK-293 cell line. During the follow-up, plasma creatinine decreased, creatinine clearance improved, and proteinuria levels recovered more rapidly in the ATI + HDL group than in the ATI group. Glucosuria remained similar across both groups throughout the study. Histological analysis revealed increased cellularity and reduced necrosis in the kidneys of the ATI + HDL group compared to ATI rats. Rats in the ATI + Lp-B group died 48 h after HgCl2 administration and tubular lesions were more severe. In vitro, HDLs effectively preserved cell viability under mercury exposure, while Lp-B did not provide similar protection. Exogenous HDLs supplementation improves biochemical markers of renal function in vivo and promotes cell survival in vitro in a HgCl2 toxicity model. These findings reveal a new beneficial property of HDLs, unlike apo B-containing lipoproteins, and underline the importance of such interventions for health support and disease management.
BACKGROUND:We present the first multicenter, non-interventional, longitudinal observational study of patients diagnosed with cardiac transthyretin amyloidosis (ATTR-CA) in Poland. AIMS:The aim of this study was to describe the clinical characteristics, survival rates, and treatment outcomes of patients with ATTR-CA in Poland, and to identify potential markers linked to an increased risk of disease progression. METHODS:Between 2017 and 2025, consecutive patients with confirmed ATTR-CA were evaluated at 4 cardiology centers. Assessments included blood tests, standard 12-lead electrocardiography, and transthoracic echocardiography. The primary endpoint was defined as death or heart transplantation. RESULTS:ATTR-CA was confirmed in 115 patients, including 21 (18.2%) with hereditary disease. The median follow-up was 24 (12-41) months for the entire cohort and 25 (14.2-46.7) months for surviving patients (n = 78). The primary endpoint occurred in 37 (32.2%) patients. In multivariable analysis, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), body mass index, and levels of high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide were independent predictors of the primary endpoint. Tafamidis was received by 81 (70.4%) patients and was associated with significantly lower risk of the primary endpoint (P = 0.005), stroke, or transient ischemic attack (P = 0.047), and a markedly longer median survival (84 months [95% confidence interval, 68-116] vs. 14 months [95% confidence interval, 7-36]; log-rank P <0.0001). In tafamidis-treated patients, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T levels remained stable at 6 and 12 months of follow-up, in contrast to untreated patients, who showed an increase in these biomarkers. CONCLUSIONS:This study provides the first multicenter data on ATTR-CA in Poland. Our findings enhance understanding of the disease course and treatment effects, underline the importance of disease-modifying therapy in improving outcomes, provide valuable real-world data on tafamidis treatment, and indicate directions for further research.
Acute exposure to hypoxia affects the cardiovascular system, especially pulmonary circulation and right heart hemodynamics. However, the impact of normobaric hypoxia on the right heart chambers during exercise is still not clear. This study examined whether a single bout of high-intensity exercise to voluntary exhaustion under acute moderate normobaric hypoxia (~3000 m a.s.l.; FiO2 = 14.4%) induces significant changes in right ventricular (RV) and right atrial (RA) dimensions or RV systolic function compared to normoxia in trained and untrained men. Twenty-four healthy males (12 trained cyclists, 12 untrained) completed randomized trials involving exhaustive exercise under normoxic and hypoxic conditions. Echocardiographic assessments were conducted at rest and post-exercise. While hypoxia was found to reduce total mechanical work, end-exercise heart rate and oxygen saturation in both groups, no differences were observed in the post-exercise RV response between normoxia and hypoxia. Only untrained men showed increased resting RV dimensions and fractional area change (FAC) in hypoxia. Both groups exhibited post-exercise declines in tricuspid annular plane systolic excursion (TAPSE), systolic tissue Doppler velocity (S' wave), and right atrial area (RAA), but no additive effect of hypoxia was observed. These results indicate that acute moderate normobaric hypoxia does not impose additional RV load during maximal exercise in healthy athletes and untrained men. Trial Registration: ClinicalTrials.gov: NCT06896773.
The prognostic role of high-risk plaque (HRP) features, including high coronary calcium scores detected by CT, beyond traditional cardiovascular risk factors and obstructive coronary artery disease (CAD), remains uncertain. This study evaluated the prognostic value of a combined HRP definition in stable chest pain patients with low-to-intermediate pretest probability of CAD. This prespecified analysis included participants randomized to the CT arm of the pragmatic, prospective 26-center European DISCHARGE trial (NCT02400229). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke); the secondary endpoint was expanded MACE (transient ischemic attack and major procedure-related complications). Our combined HRP definition was any coronary plaque with positive remodeling, napkin-ring sign, low attenuation, or total calcium score ≥ 400 Agatston units. Among 1745 participants (age: 60 ± 10 years, 990 female), 35 MACE and 47 expanded MACE occurred at a median follow-up of 3.5 years (IQR: 2.9–4.2). After risk factor adjustment, the combined HRP definition was associated with a higher risk of MACE (HR: 3.81; 95
