Atherosclerosis, characterized by lipid‐rich plaques in the arterial wall, is an age‐related disorder and a leading cause of mortality worldwide. However, the specific mechanisms remain complex. Recently, emerging evidence has demonstrated that senescence of various types of cells, such as endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages, endothelial progenitor cells (EPCs), and adipose‐derived mesenchymal stem cells (AMSCs) contributes to atherosclerosis. Cellular senescence and atherosclerosis share various causative stimuli, in which dyslipidemia has attracted much attention. Dyslipidemia, mainly referred to elevated plasma levels of atherogenic lipids or lipoproteins, or functional impairment of anti‐atherogenic lipids or lipoproteins, plays a pivotal role both in cellular senescence and atherosclerosis. In this review, we summarize the current evidence for dyslipidemia‐induced cellular senescence during atherosclerosis, with a focus on low‐density lipoprotein (LDL) and its modifications, hydrolysate of triglyceride‐rich lipoproteins (TRLs), and high‐density lipoprotein (HDL), respectively. Furthermore, we describe the underlying mechanisms linking dyslipidemia‐induced cellular senescence and atherosclerosis. Finally, we discuss the senescence‐related therapeutic strategies for atherosclerosis, with special attention given to the anti‐atherosclerotic effects of promising geroprotectors as well as anti‐senescence effects of current lipid‐lowering drugs.

Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, which is mainly characterized by lipid deposition and inflammatory response. Macrophages (MΦ), as the key mediators of the inflammatory response, run through all stages of the occurrence and development of AS, from plaque initiation to the transition to vulnerable plaques, and are regarded as important therapeutic targets. It was previously thought that the atherogenic mechanism of MΦ was mainly due to their phagocytosis of lipids, resulting in excessive foam cells aggregated on the arterial wall. However, increasing evidence has revealed the diversity of AS mechanisms caused by MΦ. For example, MΦ present a continuum phenotypic spectrum, and their polarization has been demonstrated to play a vital role in the regulation of AS-related inflammatory response. MΦ apoptosis and the ability of MΦ to clean up apoptotic cells (also known as efferocytosis) are crucial determinants of AS lesion progression and plaque stability. Hence, this review probes into the contradictory regulation of MΦ on AS based on polarization, apoptosis, and efferocytosis, designed to highlight the complex and interrelated regulated network of MΦ promoting AS.

Background: Atypical chest pain in some outpatients could derive from mental disorders. It is necessary for them to have a preliminary emotional assessment in the outpatient department of Cardiology before psychiatric outpatient visits. Methods: This study included 122 Chinese outpatients with atypical chest pain in the department of Cardiology. They accepted routine examinations, including treadmill test, and were judged by the three-question method as highly likely to have emotional disorders. Then, a standard questionnaire package containing the Chinese version of the seven-item scale for General Anxiety Disorder (GAD-7), Self-rating Anxiety Scale (SAS), the nine-item Patient Health Questionnaire (PHQ-9) and Self-rating Depression Scale (SDS) was administered to evaluate anxiety and depression. Results: The percentages of anxiety evaluated by GAD-7 and SAS were 62.3% and 26.2%, respectively. Analogously, the assessment by PHQ-9 showed a significantly higher percentage of depression than that by SDS (61.5% vs 29.5%) (P < 0.05). Kappa analysis showed that the consistency between GAD-7 and SAS, or that between PHQ-9 and SDS was not very good. About 73% outpatients suffered from emotional disorders, presenting as anxiety/depression evaluated by GAD-7 and PHQ-9. Furthermore, sleep disorders accounted for more than 80% of patients with mental disorders. Finally, the suicidal tendency of depression patients was about 17% that should not be ignored. Conclusion: Compared with SAS and SDS, GAD-7 and PHQ-9 detected more participants with emotional disorders in the Chinese outpatients with atypical chest pain, indicating that GAD-7 and PHQ-9 could be briefly well-validated tools to screen emotional disorders in the outpatient department of Cardiology before psychiatric visits.

Sufficient epidemiological investigations demonstrate that there is a close correlation between obesity and vascular dysfunction. Nevertheless, specific mechanisms underlying this link remain currently unclear. Given the crucial and decisive role of vascular dysfunction in multitudinous diseases, various hypotheses had been proposed and numerous experiments were being carried out. One recognized view is that increased adipokine secretion following the expanded mass of white adipose tissue due to obesity contributes to the regulation of vascular function. Chemerin, as a neo-adipokine, whose systemic level is elevated in obesity, is believed as a regulator of adipogenesis, inflammation, and vascular dysfunction via binding its cell surface receptor, chemR23. Hence, this review aims to focus on the up-to-date proof on chemerin/chemR23 axis-relevant signaling pathways, emphasize the multifarious impacts of chemerin/chemR23 axis on vascular function regulation, raise certain unsettled questions to inspire further investigations, and explore the therapeutic possibilities targeting chemerin/chemR23.

Abdominal aortic aneurysm (AAA) is highly lethal upon onset of acute aortic diseases (AAD) or rupture. Dyslipidaemia and hyperuricaemia are important risk factors for the development of AAA and AAD as well as aortic disease-related death. The aim of this study was to explore whether uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) can be used as an independent predictor of the presence of AAA or AAD. Three hundred subjects, including 100 AAA patients (AAA group), 100 AAD patients (AAD group) and 100 controls (CON group), were recruited in this study. UHR and other serum samples were obtained upon the patients' admission before any medical treatment. The optimal cut-off points of UHR were determined using receiver operating characteristic (ROC) curve analysis. The UHR in AAA group was significantly higher than that in CON group, but there was no significant difference between AAD group and CON group. The optimal cut-off point of UHR for AAA was 7.78 (sensitivity 84.7%, specificity 62.4%, and AUC 0.811; p < 0.001), and UHR (OR: 1.122, 95%CI: 1.064-1.184; p < 0.001) was found to be an independent factor for predicting AAA after adjusting for traditional AAA risk factor. UHR can be widely used in clinical practice as an auxiliary tool for screening AAA. The optimal cut-off point for UHR to AAA was determined for the first time in Chinese subjects.

BACKGROUND: T cells are central to the immune responses contributing to hypertension. LGMN (legumain) is highly expressed in T cells; however, its role in the pathogenesis of hypertension remains unclear. METHODS: Peripheral blood samples were collected from patients with hypertension, and cluster of differentiation (CD)4+ T cells were sorted for gene expression and Western blotting analysis. TLGMNKO (T cell–specific LGMN-knockout) mice (Lgmn ^f/f /CD4 ^Cre ), regulatory T cell (Treg)–specific LGMN-knockout mice (Lgmn ^f/f /Foxp3 ^{YFP Cre} ), and RR-11a (LGMN inhibitor)–treated C57BL/6 mice were infused with Ang II (angiotensin II) or deoxycorticosterone acetate/salt to establish hypertensive animal models. Flow cytometry, 4-dimensional label-free proteomics, coimmunoprecipitation, Treg suppression, and in vivo Treg depletion or adoptive transfer were used to delineate the functional importance of T-cell LGMN in hypertension development. RESULTS: LGMN mRNA expression was increased in CD4+ T cells isolated from hypertensive patients and mice, was positively correlated with both systolic and diastolic blood pressure, and was negatively correlated with serum IL (interleukin)-10 levels. TLGMNKO mice exhibited reduced Ang II–induced or deoxycorticosterone acetate/salt–induced hypertension and target organ damage relative to wild-type (WT) mice. Genetic and pharmacological inhibition of LGMN blocked Ang II–induced or deoxycorticosterone acetate/salt–induced immunoinhibitory Treg reduction in the kidneys and blood. Anti-CD25 antibody depletion of Tregs abolished the protective effects against Ang II–induced hypertension in TLGMNKO mice, and LGMN deletion in Tregs prevented Ang II–induced hypertension in mice. Mechanistically, endogenous LGMN impaired Treg differentiation and function by directly interacting with and facilitating the degradation of TRAF6 (tumor necrosis factor receptor–associated factor 6) via chaperone-mediated autophagy, thereby inhibiting NF-κB (nuclear factor kappa B) activation. Adoptive transfer of LGMN-deficient Tregs reversed Ang II–induced hypertension, whereas depletion of TRAF6 in LGMN-deficient Tregs blocked the protective effects. CONCLUSIONS: LGMN deficiency in T cells prevents hypertension and its complications by promoting Treg differentiation and function. Specifically targeting LGMN in Tregs may be an innovative approach for hypertension treatment.