Calcific aortic valve disease (CAVD) is the most frequent heart valve disorder. It is characterized by an active remodeling process accompanied with valve mineralization, that results in a progressive aortic valve narrowing, significant restriction of the valvular area, and impairment of blood flow.The pathophysiology of CAVD is a multifaceted process, involving genetic factors, chronic inflammation, lipid deposition, and valve mineralization. Mineralization is strictly related to the inflammatory process in which both, innate, and adaptive immunity are involved. The underlying pathophysiological pathways that go from inflammation to calcification and, finally lead to severe stenosis, remain, however, incompletely understood. Histopathological studies are limited to patients with severe CAVD and no samples are available for longitudinal studies of disease progression. Therefore, alternative routes should be explored to investigate the pathogenesis and progression of CAVD.Recently, increasing evidence suggests that epigenetic markers such as non-coding RNAs are implicated in the landscape of phenotypical changes occurring in CAVD. Furthermore, the microbiome, an essential player in several diseases, including the cardiovascular ones, has recently been linked to the inflammation process occurring in CAVD. In the present review, we analyze and discuss the CAVD pathophysiology and future therapeutic strategies, focusing on the real and putative role of inflammation, calcification, and microbiome.
Background and aimsCrohn’s disease (CD) pathogenesis is still unclear. Remodeling in mucosal microbiota and systemic immunoregulation may represent an important component in tissue injury. Here, we aim to characterize the ileal microbiota in both pathological and healthy settings and to evaluate the correlated systemic microbial-associated inflammatory markers comparing first-time surgery and relapse clinical conditions.MethodsWe enrolled 28 CD patients at surgery; we collected inflamed and non-inflamed mucosa tissues and blood samples from each patient. Bacterial wall adherence was observed histologically, while its composition was assessed through amplicon sequencing of the 16S rRNA gene. In addition, we evaluated the systemic microRNA (miRNA) using quantitative real-time PCR amplification and free fatty acids (FFAs) using gas chromatography–mass spectroscopy.ResultsThe total number of mucosal adherent microbiota was enriched in healthy compared to inflamed mucosa. In contrast, the phylum Tenericutes, the family Ruminococcaceae, and the genera Mesoplasma and Mycoplasma were significantly enriched in the pathological setting. Significant microbiota differences were observed between the relapse and first surgery patients regarding the families Bacillaceae 2 and Brucellaceae and the genera Escherichia/Shigella, Finegoldia, Antrobacter, Gemmatimonas, Moraxella, Anoxibacillus, and Proteus. At the systemic level, we observed a significant downregulation of circulating miR-155 and miR-223, as well as 2-methyl butyric, isobutyric, and hexanoic (caproic) acids in recurrence compared to the first surgery patients. In addition, the level of hexanoic acid seems to act as a predictor of recurrence risk in CD patients (OR 18; 95% confidence interval 1.24–261.81; p = 0.006).ConclusionsWe describe a dissimilarity of ileal microbiota composition comparing CD and healthy settings, as well as systemic microbial-associated inflammatory factors between first surgery and surgical relapse. We suggest that patterns of microbiota, associated with healthy ileal tissue, could be involved in triggering CD recurrence. Our findings may provide insight into the dynamics of the gut microbiota–immunity axis in CD surgical recurrence, paving the way for new diagnostics and therapeutics aimed not only at reducing inflammation but also at maintaining a general state of eubiosis in healthy tissue.
Inflammation is a physiological, beneficial and auto-limiting response of the host to alarming stimuli. Conversely, a chronic systemic low-grade inflammation (CSLGI), known as a long-time persisting condition, causes organs and host tissues’ damage, representing a major risk for chronic diseases. Currently, a worldwide a high incidence of inflammatory chronic diseases is observed, often linked to the lifestyle-related changes occurred in the last decade’s society. The mains lifestyle-related factors are a proinflammatory diet, psychological stress, tobacco smoking, alcohol abuse, physical inactivity, and finally indoor living and working with its related consequences such as indoor pollution, artificial light exposure and low vitamin D production. Recent scientific evidences found that gut microbiota (GM) has a main role in shaping the host’s health, particularly as CSLGI mediator. As a matter of facts, based on the last discoveries regarding the remarkable GM activity, in this manuscript we focused on the elements of actual lifestyle that influence the composition and function of intestinal microbial community, in order to elicit the CSLGI and its correlated pathologies. In this scenario, we provide a broad review of the interplay between modern lifestyle, GM and CSLGI with a special focus on the COVID symptoms and emerging long-COVID syndrome.
Cardiovascular diseases (CVDs), the most common cause of mortality in rich countries, include a wide variety of pathologies of the heart muscle and vascular system that compromise the proper functioning of the heart. Most of the risk factors for cardiovascular diseases are well-known: lipid disorders, high serum LDL cholesterol, hypertension, smoking, obesity, diabetes, male sex and physical inactivity. Currently, much evidence shows that: (i) the human microbiota plays a crucial role in maintaining the organism’s healthy status; and (ii) a link exists between microbiota and cardiovascular function that, if dysregulated, could potentially correlate with CVDs. This scenario led the scientific community to carefully analyze the role of the microbiota in response to drugs, considering this the right path to improve the effectiveness of disease treatment. In this review, we examine heart diseases and highlight how the microbiota actually plays a preponderant role in their development. Finally, we investigate pharmacomicrobiomics—a new interesting field—and the microbiota’s role in modulating the response to drugs, to improve their effectiveness by making their action targeted, focusing particular attention on cardiovascular diseases and on innovative potential treatments.
Calcific aortic valve disease (CAVD) is the most frequent valvular heart disorder, and the one with the highest impact and burden in the elderly population. While the quality and standardization of the current aortic valve replacements has reached unprecedented levels with the commercialization of minimally-invasive implants and the design of procedures for valve repair, the need of supplementary therapies able to block or retard the course of the pathology before patients need the intervention is still awaited. In this contribution, we will discuss the emerging opportunity to set up devices to mechanically rupture the calcium deposits accumulating in the aortic valve and restore, at least in part, the pliability and the mechanical function of the calcified leaflets. Starting from the evidences gained by mechanical decalcification of coronary arteries in interventional cardiology procedures, a practice already in the clinical setting, we will discuss the advantages and the potential drawbacks of valve lithotripsy devices and their potential applicability in the clinical scenario.
Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process: namely, valve fibrosis with its area narrowing, impaired blood flow, and final calcification phase. Nowadays, the only treatment is the surgical valve replacement. As for other cardiovascular diseases, growing evidence suggest an active role of the immune system in the calcification process that could be modulated by the microbiota. To address this point, we aimed to investigate and characterize, for the first time, the presence of a valve microbiota and associated immune response in human CAVD. Method: Calcified aortic valve (CAV) samples from twenty patients (11 from Germany and 9 from Italy) with diagnosis of severe symptomatic CAVD were used to assess the presence of infiltrating T cells, by cloning approach, and to characterize the valve microbiota, by 16S rRNA gene sequencing (NGS). Results: We documented the presence of infiltrating T lymphocytes, especially the T helper subset, in CAV samples. Moreover, we found a tissue-associated microbiota in freshly collected CAV samples, which was significantly different in Italian and German patients, suggesting potential correlation with other cardiovascular risk factors. Conclusion: The presence of microbiota in inflamed CAV samples represents the right trigger point to explain the valve calcification process, encouraging further studies to explore the potential link between bacteria and adaptive immune response and to define the critical role of local microbiota-immunity axis on CAVD development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.