Age-related atrial fibrillation (AF) is a common condition that has yet to be fully understood, with mechanisms to explain its development under investigation. Notably, cellular senescence, cardiac fibrosis, coronary ischemia, cardiac valvular disease, autonomic dysfunction, channelopathies, and immune system remodeling are processes that have been seen to occur with aging and ample evidence has shown their association with the development of AF. Despite robust therapeutic approaches, the incidence of AF continues to rise, suggesting that the dynamic, multi-faceted interactions leading to AF are incompletely understood. One of the newer mechanisms currently being investigated is the gut microbiome. Although more research is needed to understand its impact on the development of age-related AF and targets for therapies, the gut microbiome is a promising new avenue of research that may provide future benefits in AF prophylaxis or enhanced management. As the field works towards developing this knowledge, there are important questions to answer as to the optimal role of potential gut microbiome targeting therapies and their potential risks versus the benefits they provide. This commentary first summarizes the currently understood mechanisms contributing to age-related AF, which is then followed by an analysis of the current work investigating the role of the gut microbiome in the development of age-related AF, and concludes by highlighting notable questions to consider in future work on the role of the gut microbiome and its relationship to age-related AF.

The oxidation of lipoproteins has a key role in the development of atherosclerosis, a condition where plaque builds up in artery walls. Research shows that when low-density lipoprotein (LDL) oxidizes, it speeds up atherosclerosis. Oxidized LDL (Ox-LDL) causes many pathologic scenarios that lead to atherosclerosis. It was suggested as a fundamental player in endothelial dysfunction, creating foam cells, and triggering inflammation in artery walls. How Ox-LDL contributes and interacts with specific receptors on endothelial cells is crucial to these effects. This article aims to shed light on LDL oxidation, the stages of the process, and how Ox-LDL promotes atherosclerosis. A comprehensive search was conducted across various databases, including PubMed, Google Scholar, Scopus, and Ovid, to identify literature and studies that discuss Ox-LDL and their involvement in the pathogenesis of atherosclerosis and cardiovascular diseases, thereby establishing a well-defined perspective on the subject. This review will provide a closer look at the Ox-LDL particle, the different forms and stages of oxidation, and the role of various LDL receptors involved in LDL uptake and breakdown focusing on how they contribute to atherosclerosis. Then, it will discuss the role of scavenger receptors and their contribution to the uptake of Ox-LDL and how this contributes to the development of atherosclerosis.

Vascular aging is recognized as one of the hallmarks of atherosclerosis. Currently, a growing body of evidence suggests that there exists a mutual crosstalk between telomere dysfunction and mitochondrial dysmetabolism during the process of vascular senescence. This underscores the importance of comprehensively studying the molecular mediators involved in this complex and intricate connection. In pursuit of this goal, the “VICTORIA” protocol entails a prospective single-center cohort study aimed at recruiting patients undergoing coronary angiography at Niguarda Hospital in Italy. The primary objective is to explore potential associations between peripheral markers of cell aging (telomere length and mtDNA content), dysregulation of non-coding RNA [specifically lncRNA TERRA and mitochondrial microRNA (MitomiR)], and the varied presentations of ischemic heart disease (stable angina, unstable angina, NSTEMI, and STEMI). Furthermore, we aim to investigate whether these markers correlate with vulnerable plaque characteristics, as assessed by optical coherence tomography findings. Additionally, systemic levels of pro-inflammatory biomarkers and novel indicators of senescence will be assessed. Patients will be followed up at 1 year to monitor primary outcomes including mortality, myocardial infarction, stroke, unplanned revascularization, and rehospitalization. The anticipated findings of this study hold promise for advancing our understanding of the telomere-mitochondria crosstalk, potentially paving the way for novel treatment modalities and refined risk stratification approaches for acute coronary syndrome.

Metabolic syndrome (MetS) is known as a non-communicable disease (NCD) that affects more and more individuals. MetS is closely related to type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), obesity and inflammation. It is associated with T2DM due to the disturbance in insulin secretion/effect, eventually leading to insulin resistance (IR). The link between MetS and CVD is due to accelerated atherosclerosis in response to chronic inflammation. This literature review was based on a search in the PubMed database. All selected articles are written in English and cover a period of approximately 10 years (January 2014 to May 2023). The first selection used MeSH terms such as: “metabolic syndrome”, “type 2 diabetes mellitus”, “obesity”, “inflammation”, and “insulin resistance” and different associations between them. Titles and abstracts were analyzed. In the end, 44 articles were selected, 4 of which were meta-analysis studies. Currently, an individual is considered to have MetS if they present 3 of the following changes: increased waist circumference, increased triglycerides (TG), reduced high-density lipoprotein cholesterol (HDL-C), increased fasting blood glucose and hypertension. We believe this can often lead to a false diagnosis. The objective of this paper is to compile what we consider to be an appropriate panel of MetS indicators. The markers that stand out in this review are the lipid profile, anti- and pro-inflammatory function and oxidative stress. Considering the research, we believe that a complete panel, to correlate the most characteristic conditions of MetS, should include the following markers: TG/HDL-C ratio, small dense low-density lipoprotein cholesterol (SdLDL-C), lipid peroxidation markers, leptin/adiponectin ratio, plasminogen activator inhibitor-1 (PAI-1), activin-A and ferritin levels. Finally, it is important to expand research on the pathophysiology of MetS and confirm the most appropriate markers as well as discover new ones to correctly diagnose this condition.