Cardiovascular diseases (CVD) remain the leading cause of death worldwide, with advancing age being the primary, nonmodifiable risk factor. Vascular dysfunction, namely arterial stiffening and endothelial dysfunction, is the key antecedent to the development of clinical CVD with aging. Fundamental aging macro-mechanistic processes that drive vascular aging include excess oxidative stress, chronic inflammation, and declines in the vasodilatory molecule nitric oxide. An important hallmark of aging that contributes to the vascular aging processes is cellular senescence - a stress response characterized by cell cycle arrest and accompanied by the production and secretion of proinflammatory molecules (i.e., the senescence-associated secretory phenotype [SASP]). Excess senescent cells and the SASP have deleterious effects on vascular function and in states of CVD, making it a putative therapeutic target for improving vascular function and preventing or reversing CVD. This review will focus on the role of cellular senescence in age-related vascular dysfunction and CVD. We will examine established and emerging mechanisms underlying cellular senescence-induced vascular dysfunction. We will then discuss groups with impaired vascular function and high cellular senescence burden and examine strategies to reduce or remove excess senescent cells and the SASP in the groups who are likely to benefit most from these therapies. Finally, we will highlight the systemic effects of vascular senescent cell suppression on other tissues and organs, given the integrative role of the vasculature in physiology. Together, this review will underscore the imperative role of cellular senescence in vascular dysfunction and the need for a deeper understanding of the translational use of cellular senescence and SASP targeting therapies in groups with high senescent cell burden.

Aging is a primary driver of atrial remodeling and dysfunction, and contributes to the increasing prevalence of atrial myopathy in the aging population. Atrial myopathy, characterized by structural, functional, and electrophysiological abnormalities of the atria, is a key pathological process underlying adverse cardiovascular outcomes such as atrial fibrillation (AF), heart failure with preserved ejection fraction (HFpEF), and ischemic stroke. Although these outcomes are often treated as distinct clinical entities, emerging evidence suggests that they may represent symptomatic manifestations of an underlying atrial disease process. Aging promotes atrial myopathy through multiple mechanisms, including inflammation, extracellular matrix remodeling, electrophysiological alterations, cellular senescence, epigenetic modifications, and non-coding RNA regulation. These changes collectively lead to atrial fibrosis, impaired mechanical function, conduction abnormalities, and a prothrombotic state. Despite its clinical significance, atrial myopathy remains an underrecognized entity, with current management strategies primarily focusing on treating its downstream complications rather than the underlying disease. Advances in imaging techniques, biomarker discovery, and molecular research have the potential to improve the early detection and risk stratification of atrial myopathy, paving the way for novel therapeutic strategies. In this review, we discuss the structural, mechanical, electrophysiological, and metabolic changes that occur in the aging atrium, explore the cellular and molecular mechanisms that drive these changes, and highlight recent advances in diagnostic and therapeutic approaches. By shifting the focus from managing AF and HFpEF to targeting the underlying atrial myopathy, we can unlock new avenues for prevention and treatment, ultimately improving cardiovascular health in the aging population.

Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, and is driven by molecular and cellular mechanisms described in the hallmarks of aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, also mediates processes like vascular stiffness, cellular senescence, and immune evasion. This review highlights PAI-1’s role in cardiovascular aging with a special emphasis on senescence, a key hallmark of aging. It further explores PAI-1’s therapeutic potential, with a focus on its contribution to ECM remodeling, senescence signaling, and immune checkpoint regulation. Targeting PAI-1 could provide a promising strategy to mitigate age-related cardiovascular disease.

This review aims to summarize the current landscape of cardiac arrhythmia therapeutics and highlight recent advances in nanoparticle-based strategies for the treatment of various human cardiac arrhythmias. A comprehensive literature review was conducted to curate and synthesize recent preclinical developments in nanoparticle-mediated therapies targeting cardiac arrhythmias. Cardiac arrhythmias represent one of the most prevalent and challenging forms of cardiovascular disease worldwide. Conventional treatments, including antiarrhythmic drugs, are often limited by suboptimal efficacy, high recurrence rates, and significant off-target toxicities. While catheter-based ablation techniques have emerged as alternative interventions, their long-term success remains inconsistent, as highlighted by outcomes from large trials such as the CABANA trial. In response to these limitations, nanoparticle-based interventions have emerged as a promising class of therapeutics. These strategies offer potential advantages, including site-specific drug delivery, reduced systemic toxicity, and novel approaches to both pharmacologic and ablative therapy. This review presents an overview of the emerging nanoparticle-based strategies for the treatment of atrial fibrillation and other cardiac arrhythmias. It also discusses recent proof-of-concept studies, evaluates the benefits and limitations of various nanoparticle formulations, and outlines key challenges and future directions for translating these technologies into clinical practice.

Aging alters the immune system, leading to immunosenescence characterized by impaired T cell functions. The balance between regulatory T cells and type 17 helper T (Th17) cells is crucial for maintaining peripheral immune homeostasis. Aging disrupts this balance, contributing to a systemic chronic proinflammatory environment that increases the prevalence of age-related diseases. The Treg/Th17 imbalance compromises self-tolerance, promoting autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Furthermore, chronic inflammation driven by aberrant T cell responses is a significant risk factor for the progression of cardiovascular diseases (CVD), including hypertension, atherosclerosis, myocardial infarction, and myocarditis. Autoimmune disorders further exacerbate the risk of CVD, which remains the leading cause of mortality among patients with autoimmune diseases. This review provides an in-depth analysis of the mechanisms driving Treg/Th17 imbalance during aging, highlighting its impact on immune homeostasis, autoimmunity, and cardiovascular health. It explores how inflammaging and T cell dysfunction contribute to diseases such as rheumatoid arthritis, systemic lupus erythematosus, atherosclerosis, and myocardial infarction, emphasizing shared pathways and therapeutic strategies to restore immune balance and mitigate chronic inflammation. Understanding these immune pathways highlights the therapeutic potential of restoring Treg/Th17 balance to restore immune tolerance and reduce chronic inflammation, thereby mitigating the onset and progression of these age-related conditions.

Hypertrophic cardiomyopathy (HCM) is a highly common cardiomyopathy and is characterized by left ventricular hypertrophy and diastolic dysfunction. In half of the cases, HCM is associated with mutations in genes encoding sarcomere proteins, while the remaining cases occur without identifiable genetic mutations. Disrupted bioenergetic homeostasis has increasingly been recognized as a key feature of HCM pathophysiology. In this review, we summarize and critically evaluate studies addressing cardiometabolic alterations in HCM, with a particular focus on human-based research. These include non-invasive imaging studies, blood-based analyses, and molecular and functional assays of myocardial tissue. We also explore the therapeutic potential of targeting metabolic pathways in HCM and highlight promising directions for future studies.

Introduction: The link between low-density lipoprotein/high-density lipoprotein (LDL/HDL ratio, LHR) and the prevalence of hypertension in large populations, especially among individuals aged 20 and older, has not been extensively explored. This research aims to examine whether LHR is associated with hypertension prevalence.

Methods: This retrospective cohort analysis drew on cross-sectional data from a health check-up database located in China. Hypertension is classified as a systolic blood pressure (SBP) of ≥ 140 mmHg or a diastolic blood pressure (DBP) of ≥ 90 mmHg. Multivariable logistic regression was used to examine the association between LHR and hypertension prevalence. Furthermore, a subgroup analysis was performed to assess how this association varied across different demographic categories.

Results: The cross-sectional evaluation encompassed 113,912 participants. After adjusting for confounding variables, every unit rise in LHR correlated with an 11% increase in the prevalence of hypertension (Odds Ratio [OR] = 1.11, 95% Confidence Interval [CI]: 1.06, 1.16). Our findings indicated a nonlinear relationship between LHR and hypertension prevalence, with an inflection point at 2.28. Below this level, each unit increase in LHR was linked to a 168% heightened risk of hypertension, while above this point, the correlation became insignificant. The subgroup analysis indicated that females, older adults, non-smokers, and individuals with lower body mass index (BMI) exhibited a particularly high prevalence of hypertension associated with higher LHR levels.

Conclusion: The findings suggest that a higher LHR serves as a notable predictor of hypertension and elevated blood pressure among Chinese adults aged 20 and older. The identified nonlinear relationship and threshold effect highlight the importance of LHR in hypertension screening and management.

Myocardial infarction (MI), commonly known as a heart attack, results from the rupture of atherosclerotic plaques in coronary arteries, which triggers a series of pathological events including cardiomyocyte death, thrombus formation, and systemic inflammation. These pathological events lead to significant structural and functional changes in the heart, potentially precipitating heart failure. The ramifications of MI extend beyond cardiac dysfunction and impact cerebral health. Accordingly, this review examines the cerebral implications of MI, focusing on how systemic inflammation and reduced cardiac output post-MI affect cerebral blood flow and brain function. MI-induced changes in cardiac output can lead to cerebral hypoperfusion, while neuroinflammation and increased blood-brain barrier permeability contribute to cognitive decline and neuronal damage, with potential links to Alzheimer's disease (AD). Furthermore, the review explores the role of estrogen in modulating cardiovascular and cerebral health, particularly in postmenopausal women who exhibit distinct cardiovascular risk profiles. Estrogen protects the heart by regulating local renin-angiotensin-aldosterone system and has significant impacts on brain function. Declining estrogen levels during menopause exacerbate neuroinflammation and cognitive deficits, highlighting the importance of estrogen in maintaining cerebrovascular function. Experimental studies on estrogen replacement therapies, including 17β-estradiol and selective estrogen receptor modulators, show potential in mitigating these detrimental effects, enhancing neurogenesis, and improving cognitive outcomes. Estrogen therapy is crucial in preventing cognitive decline and reducing amyloid plaque formation in Alzheimer's models. This review underscores the potential benefits of estrogen therapy in promoting brain recovery post-MI and improving functional outcomes.