ABSTRACT
The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages, which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased postinfection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting toward an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.
Subject(s)
COVID-19 , Osteoclasts , Humans , Osteoclasts/metabolism , Post-Acute COVID-19 Syndrome , COVID-19/metabolism , SARS-CoV-2 , Cell DifferentiationABSTRACT
Current evidence reveals that cardiac mineralocorticoid receptor (MR) activation following myocardial stretch plays an important physiological role in adapting developed force to sudden changes in hemodynamic conditions. Its underlying mechanism involves a previously unknown nongenomic effect of the MR that triggers redox-mediated Na+/H+ exchanger (NHE1) activation, intracellular Na+ accumulation, and a consequent increase in Ca2+ transient amplitude through reverse Na+/Ca2+ exchange. However, clinical evidence assigns a detrimental role to MR activation in the pathogenesis of severe cardiac diseases such as congestive heart failure. This mini review is meant to present and briefly discuss some recent discoveries about locally triggered cardiac MR signals with the objective of shedding some light on its physiological but potentially pathological consequences in the heart.
ABSTRACT
BACKGROUND: The aim of this study was to evaluate gender-associated impact on left ventricular mass (LVM) and on left ventricular function (LVF) in humans and rats with aging. METHODS: Myocyte area and collagen volume fraction (CVF) were studied in rats. LVM and LVF were evaluated in animals and humans by echocardiography and LVM index (LVMI) was obtained. RESULTS: LVMI, myocyte area and CVF were similar in males and females of 1-month-old rats. LVMI in children was similar in both genders. In contrast, in 6-month-old rats (5 males and 5 females), LVMI (17.7 ± 0.7 mg/mm vs. 10.1 ± 0.2 mg/mm; p < 0.01), and myocyte area (4572.5 ± 72.6 µm² vs. 3293.85 ± 57.8 µm², p < 0.01) were higher in male animals without differences in CVF. Men (n = 25) exhibited greater LVMI than women (n = 25) (77.4 ± 3.2 g/m² vs. 63.3 ± 1.8 g/m², p < 0.01), whereas the LVF was higher in women (105.9 ± 2.9% vs. 95.3 ± 3.5%, p < 0.01). CONCLUSIONS: There is a clear gender-associated impact on LVM with aging in humans and rats. Similar CVF and LVF associated to greater myocyte size and LVM in male rats suggest a process of physiological response. However, the increase in cardiac mass without an associated improved cardiac function in men in comparison to women could likely represent a potential disadvantage in the adaptive response during growth.
