Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a crucial role in extracellular matrix (ECM) remodeling and are implicated in the pathogenesis of various cardiovascular diseases (CVDs). Their dysregulation has been linked to atherosclerosis, myocardial infarction (MI), heart failure (HF), and aortic stenosis, contributing to vascular inflammation, plaque destabilization, and adverse cardiac remodeling. Recent research highlights MMPs’ involvement beyond ECM degradation, influencing lipoprotein metabolism, inflammatory signaling, and intracellular processes critical for cardiovascular homeostasis. Despite their pathological role, MMPs remain promising therapeutic targets, with pharmacological inhibitors, gene therapy, and tissue inhibitors of metalloproteinases (TIMPs) emerging as potential interventions. However, the clinical translation of MMP-targeting therapies remains challenging due to off-target effects and complex regulatory mechanisms. This review provides an updated synthesis of the molecular mechanisms, disease-specific roles, and therapeutic implications of MMPs in cardiovascular pathology, aiming to bridge the gap between fundamental research and clinical applications.

We are witnessing the globalization of a specific type of arteriosclerosis with rising prevalence, incidence and an overall cardiovascular disease burden. Currently, atherosclerosis increasingly affects the younger generation as compared to previous decades. While early preventive medicine has seen improvements, research advances in laboratory and clinical investigation promise to provide us with novel diagnosis tools. Given the physio-pathological complexity and epigenetic patterns of atherosclerosis and the discovery of new molecules involved, the therapeutic field of atherosclerosis has room for substantial growth. Thus, the scientific community is currently investigating the role of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a crucial component of the innate immune system in different inflammatory disorders. NLRP3 is activated by distinct factors and numerous cellular and molecular events which trigger NLRP3 inflammasome assembly with subsequent cleavage of pro-interleukin (IL)-1β and pro-IL-18 pathways via caspase-1 activation, eliciting endothelial dysfunction, promotion of oxidative stress and the inflammation process of atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation and its role in atherosclerosis. We also emphasize its promising therapeutic pharmaceutical potential.

Calcific aortic valve disease (CAVD) is a major cause of cardiovascular mortality and morbidity, with increased prevalence and incidence. The underlying mechanisms behind CAVD are complex, and are mainly illustrated by inflammation, mechanical stress (which induces prolonged aortic valve endothelial dysfunction), increased oxidative stress (OS) (which trigger fibrosis), and calcification of valve leaflets. To date, besides aortic valve replacement, there are no specific pharmacological treatments for CAVD. In this review, we describe the mechanisms behind aortic valvular disease, the involvement of OS as a fundamental element in disease progression with predilection in AS, and its two most frequent etiologies (calcific aortic valve disease and bicuspid aortic valve); moreover, we highlight the potential of OS as a future therapeutic target.

Branched-chain amino acids (BCAAs), comprising leucine (Leu), isoleucine (Ile), and valine (Val), are essential nutrients vital for protein synthesis and metabolic regulation via specialized signaling networks. Their association with cardiovascular diseases (CVDs) has become a focal point of scientific debate, with emerging evidence suggesting both beneficial and detrimental roles. This review aims to dissect the multifaceted relationship between BCAAs and cardiovascular health, exploring the molecular mechanisms and clinical implications. Elevated BCAA levels have also been linked to insulin resistance (IR), type 2 diabetes mellitus (T2DM), inflammation, and dyslipidemia, which are well-established risk factors for CVD. Central to these processes are key pathways such as mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-light-chain-enhancer of activate B cells (NF-κB)-mediated inflammation, and oxidative stress. Additionally, the interplay between BCAA metabolism and gut microbiota, particularly the production of metabolites like trimethylamine-N-oxide (TMAO), adds another layer of complexity. Contrarily, some studies propose that BCAAs may have cardioprotective effects under certain conditions, contributing to muscle maintenance and metabolic health. This review critically evaluates the evidence, addressing the biological basis and signal transduction mechanism, and also discusses the potential for BCAAs to act as biomarkers versus active mediators of cardiovascular pathology. By presenting a balanced analysis, this review seeks to clarify the contentious roles of BCAAs in CVD, providing a foundation for future research and therapeutic strategies required because of the rising prevalence, incidence, and total burden of CVDs.

Diabetic retinopathy (DR), a leading cause of vision impairment worldwide, is characterized by progressive damage to the retina due to prolonged hyperglycemia. Despite advances in treatment, current interventions largely target late-stage vascular complications, leaving underlying neurodegenerative processes insufficiently addressed. This article explores the crucial role in neuronal survival, axonal growth, and synaptic plasticity and the neuroprotective potential of Brain-Derived Neurotrophic Factor (BDNF) as a therapeutic strategy for enhancing retinal resilience in DR. Furthermore, it discusses innovative delivery methods for BDNF, such as gene therapy and nanocarriers, which may overcome the challenges of achieving sustained and targeted therapeutic levels in the retina, focusing on early intervention to preserve retinal function and prevent vision loss.

Oral microbiota formation begins from birth, and everything from genetic components to the environment, alongside the host’s behavior (such as diet, smoking, oral hygiene, and even physical activity), contributes to oral microbiota structure. Even though recent studies have focused on the gut microbiota’s role in systemic diseases, the oral microbiome represents the second largest community of microorganisms, making it a new promising therapeutic target. Periodontitis and dental caries are considered the two main consequences of oral bacterial imbalance. Studies have shown that oral dysbiosis effects are not limited locally. Due to technological advancement, research identified oral bacterial species in heart valves. This evidence links oral dysbiosis with the development of valvular heart disease (VHD). This review focuses on describing the mechanism behind prolonged local inflammation and dysbiosis, that can induce bacteriemia by direct or immune-mediated mechanisms and finally VHD. Additionally, we highlight emerging therapies based on controlling oral dysbiosis, periodontal disease, and inflammation with immunological and systemic effects, that exert beneficial effects in VHD management.