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Background/Objectives: Aging is associated with structural and functional changes in the heart, including hypertrophy, fibrosis, and impaired contractility. Cellular mechanisms such as senescence, telomere shortening, and DNA damage contribute to these processes. Nuclear factor kappa B (NF-κB) has been implicated in mediating cellular responses in aging tissues, and increased NF-κB expression has been observed in the hearts of aging rodents. Therefore, NF-κB is suspected to play an important regulatory role in the cellular and molecular processes occurring in the heart during aging. This study investigates the in vivo role of NF-κB in aging-related cardiac alterations, focusing on senescence and associated cellular events. Methods: Young and old wild-type (WT) and transgenic male mice with cardiomyocyte-specific NF-κB suppression (3M) were used to assess cardiac function, morphology, senescence markers, lipofuscin deposition, DNA damage, and apoptosis. Results: Kaplan–Meier analysis revealed reduced survival in 3M mice compared to WT. Echocardiography showed evidence of eccentric hypertrophy, and both diastolic and systolic dysfunction in 3M mice. Both aged WT and 3M mice exhibited cardiac hypertrophy, with more pronounced hypertrophic changes in cardiomyocytes from 3M mice. Additionally, cardiac fibrosis, senescence-associated β-galactosidase activity, p21 protein expression, and DNA damage (marked by phosphorylated H2A.X) were elevated in aged WT and both young and aged 3M mice. Conclusions: The suppression of NF-κB in cardiomyocytes leads to pronounced cardiac remodeling, dysfunction, and cellular damage associated with the aging process. These findings suggest that NF-κB plays a critical regulatory role in cardiac aging, influencing both cellular senescence and molecular damage pathways. This has important implications for the development of therapeutic strategies aimed at mitigating age-related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM), a major component of air pollution, is associated with the development of cardiovascular diseases (CVDs). Cellular senescence and other aging mechanisms are also key factors in the development and progression of CVD. This study aims to investigate age-related susceptibility to cardiac remodeling and senescence due to PM exposure. Methods: Young and old male C57BL/6 mice were exposed to filtered or polluted air for six months using an ambient particle concentrator. Cardiac hypertrophy, fibrosis, and markers of cellular senescence (p53, p21, p-H2AX, and lipofuscin) in the myocardium were evaluated in the experimental groups. Results: PM exposure induces signs of cardiac remodeling, including cardiomyocyte enlargement and increased fibrosis, in young mice, along with elevated p53 expression. However, no significant alterations in cardiac structure or senescence markers were observed between aged mice exposed or not to PM. Conclusions: Our study indicates that younger individuals may be more vulnerable to the cardiovascular effects of chronic PM than older individuals exposed later. Further studies are needed to explore detailed mechanisms of this age-dependent response. [ABSTRACT FROM AUTHOR]

Megacities can be considered excellent laboratories for studying the effects of the urban environment on human health. Typically, exposure to pollution is estimated according to daily or annual averages of pollutant concentrations, collected at monitoring stations, using satellite data for remote sensing of pollutant levels, considering proximity to major roads, or through personal exposure monitoring with portable sensors. However, these approaches fall short in identifying individual exposure values over a lifetime. It is well established that individuals living in large urban areas inhale atmospheric particles containing carbonaceous components, resulting in the deposition of black pigments in lung tissue, known as black carbon or anthracosis. This study aims to detail the procedures for assessing the deposition of such pigments, which serve as an estimate of an individual's exposure to atmospheric pollution particles. Data collection involves administering detailed questionnaires and capturing lung images in the autopsy room. The analysis is based on macroscopic quantification of black pigments, supplemented by an evaluation of personal habits and the clinical histories of the individuals. This method of estimating lifetime exposure to inhaled particles provides a valuable tool for understanding the correlation between urban living and its potential health effects. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that calcium-binding protein S100A8 and myeloid differentiation factor-88 (MyD88) are important mediators of nuclear transcription factor kappa-B (NF-κB) activation in cardiomyocytes and that signalling molecules are involved in the hypertrophic response that is stimulated by thyroid hormones (TH). Angiotensin II (Ang II), the main active peptide of the renin-angiotensin system (RAS), binds to type 1 Ang II receptor (AT1R) and subsequently promotes cardiac hypertrophy and the inflammatory response with NF-κB activation underlying the cardiovascular effects. Considering the amount of evidence that RAS is an important mediator of TH actions on the cardiovascular system, we aimed to investigate whether cardiac expression of NF-κB and upstream associated molecules could be altered in hyperthyroidism, as well as whether AT1R could mediate the effects of TH on cardiac tissue and in cardiomyocytes in culture. Wistar rats were subjected to hyperthyroidism with or without the AT1R blocker losartan. The TH serum levels, haemodynamic parameters and cardiac mass were assessed to confirm the hyperthyroid status. The S100A8, MyD88 and nuclear NF-κB expression levels were increased in the hearts of the hyperthyroid rats, and the losartan treatment attenuated these TH effects. In addition, the cultured cardiomyocytes that had been stimulated with losartan exhibited blunted S100A8 upregulation and NF-κB activation compared with the TH-treated cells. Together, our results suggest that AT1R participates in TH-induced cardiac hypertrophy partly by mediating S100A8, MyD88 and NF-κB activation via TH. These findings indicate the important crosstalk between TH and RAS, highlighting the participation of AT1R in the triggered mechanisms of TH that contribute to the cardiac hypertrophy response. [ABSTRACT FROM AUTHOR]

The angiotensin II type 1 receptor (AT1R) is involved in the development of cardiac hypertrophy promoted by thyroid hormone. Recently, we demonstrated that triiodothyronine (T3) rapidly increases AT1R mRNA and protein levels in cardiomyocyte cultures. However, the molecular mechanisms responsible for these rapid events are not yet known. In this study, we investigated the T3 effect on AT1R mRNA polyadenylation in cultured cardiomyocytes as well as on the expression of microRNA-350 (miR-350), which targets AT1R mRNA. The transcriptional and translational actions mediated by T3 on AT1R levels were also assessed. The total content of ubiquitinated proteins in cardiomyocytes treated with T3 was investigated. Our data confirmed that T3 rapidly raised AT1R mRNA and protein levels, as assessed by realtime PCR and western blotting respectively. The use of inhibitors of mRNA and protein synthesis prevented the rapid increase in AT1R protein levels mediated by T3. In addition, T3 rapidly increased the poly-A tail length of the AT1R mRNA, as determined by rapid amplification of cDNA ends poly-A test, and decreased the content of ubiquitinated proteins in cardiomyocytes. On the other hand, T3 treatment increased miR-350 expression. In parallel with its transcriptional and translational effects on the AT1R, T3 exerted a rapid posttranscriptional action on AT1R mRNA polyadenylation, which might be contributing to increase transcript stability, as well as on translational efficiency, resulting to the rapid increase in AT1R mRNA expression and protein levels. Finally, these results show, for the first time, that T3 rapidly triggers distinct mechanisms, which might contribute to the regulation of AT1R levels in cardiomyocytes. [ABSTRACT FROM AUTHOR]