Cardiovascular Disease Cell Research Articles

The Role of Stem Cells in the Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are the leading cause of death and include several vascular and cardiac disorders, such as atherosclerosis, coronary artery disease, cardiomyopathies, and heart failure. Multiple treatment strategies exist for CVDs, but there is a need for regenerative treatment of damaged heart. Stem cells are a broad variety of cells with a great differentiation potential that have regenerative and immunomodulatory properties. Multiple studies have evaluated the efficacy of stem cells in CVDs, such as mesenchymal stem cells and induced pluripotent stem cell-derived cardiomyocytes. These studies have demonstrated that stem cells can improve the left ventricle ejection fraction, reduce fibrosis, and decrease infarct size. Other studies have investigated potential methods to improve the survival, engraftment, and functionality of stem cells in the treatment of CVDs. The aim of the present review is to summarize the current evidence on the role of stem cells in the treatment of CVDs, and how to improve their efficacy.

Role and mechanism of miRNA in cardiac microvascular endothelial cells in cardiovascular diseases.

The occurrence and development of myocardial dysfunction are associated with damage in the cardiac microvascular endothelial cells (CMECs), which can regulate nutrient exchange and oxy-gen-carbon cycling to protect cardiomyocytes. Interventions targeting microRNAs (miRNAs) can effectively mitigate CMEC injury and thus improve cardiovascular diseases. MiRNAs are a class of noncoding single-strand RNA molecules typically 21-23 nucleotides in length that are encoded by endogenous genes. They are critical regulators of organism development, cell differentiation, metabolism, and apoptosis. Current clinical trials on miRNA drugs indicate that patient-specific miRNA levels are now being used as one of the criteria for predicting heart disease. However, the cellular process of various miRNAs in CMECs in cardiovascular diseases has not been fully elucidated. These mechanisms are a field that immediately requires further investigation. Accordingly, this review summarizes the roles and mechanisms of various miRNAs in CMECs in cardiovascular disease and includes the process of CMEC crosstalk between miRNAs and other cell types in the heart. Our study serves as a theoretical basis for the formal introduction of miRNA use into the treatment of cardiovascular diseases in the future.

Causal roles of immune cells in cardiovascular diseases: A Mendelian randomization (MR) study.

Despite being a major global cause of mortality, the exact underlying mechanisms of cardiovascular diseases (CVDs) remain uncertain. This study aimed to elucidate the possible pathological connection between circulating activated immune cell types and the advancement of CVD. A two-sample Mendelian randomization analysis was performed on publicly available genetic databases to examine the potential causal relationships among 731 immune phenotypes and CVD risks. The study focused on four distinct immune signatures: relative cell counts (RC), absolute cell counts (AC), morphological parameters (MP), and median fluorescence intensities (MFI). A sensitivity analysis was performed to assess the findings' consistency, robustness, and potential pleiotropic effects. Significant associations between CVD and various immunophenotypes were observed in this study. Specifically, two phenotypes exhibited protective effects against CVD. The odds ratio (OR) for activated and secretory CD4+ regulatory T-cells (Tregs) was 0.757 [95% confidence interval (CI): 0.628-0.913; p = 0.004], whereas that for B-cell activating factor receptor on IgD-CD38+ memory B-cells was 0.654 (95% CI: 0.468-0.915; p = 0.013). Conversely, three major immunophenotypes were linked to heightened risks of CVD: CD80 on myeloid dendritic cells (OR: 1.181; 95% CI: 1.015-1.376; p = 0.032), the proportion of CD28+ CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.064; 95% CI: 1.002-1.128; p = 0.041), and the proportion of CD28-CD45RA+ CD8+ T-cells in total T-cell population (OR: 1.005; 95% CI: 1.000-1.011; p = 0.045). This study underscores significant correlations between specific immune phenotypes and the risks associated with CVD onset, thus providing valuable perspectives for forthcoming clinical inquiries.

Metabolism Serves as a Bridge Between Cardiomyocytes and Immune Cells in Cardiovascular Diseases.

Metabolic disorders of cardiomyocytes play an important role in the progression of various cardiovascular diseases. Metabolic reprogramming can provide ATP to cardiomyocytes and protect them during diseases, but this transformation also leads to adverse consequences such as oxidative stress, mitochondrial dysfunction, and eventually aggravates myocardial injury. Moreover, abnormal accumulation of metabolites induced by metabolic reprogramming of cardiomyocytes alters the cardiac microenvironment and affects the metabolism of immune cells. Immunometabolism, as a research hotspot, is involved in regulating the phenotype and function of immune cells. After myocardial injury, both cardiac resident immune cells and heart-infiltrating immune cells significantly contribute to the inflammation, repair and remodeling of the heart. In addition, metabolites generated by the metabolic reprogramming of immune cells can further affect the microenvironment, thereby affecting the function of cardiomyocytes and other immune cells. Therefore, metabolic reprogramming and abnormal metabolite levels may serve as a bridge between cardiomyocytes and immune cells, leading to the development of cardiovascular diseases. Herein, we summarize the metabolic relationship between cardiomyocytes and immune cells in cardiovascular diseases, and the effect on cardiac injury, which could be therapeutic strategy for cardiovascular diseases, especially in drug research.

Research hotspots and emerging trends of mesenchymal stem cells in cardiovascular diseases: a bibliometric-based visual analysis.

Mesenchymal stem cells (MSCs) have important research value and broad application prospects in cardiovascular diseases (CVDs). However, few bibliometric analyses on MSCs in cardiovascular diseases are available. This study aims to provide a thorough review of the cooperation and influence of countries, institutions, authors, and journals in the field of MSCs in cardiovascular diseases, with the provision of discoveries in the latest progress, evolution paths, frontier research hotspots, and future research trends in the regarding field. The articles related to MSCs in cardiovascular diseases were retrieved from the Web of Science. The bibliometric study was performed by CiteSpace and VOSviewer, and the knowledge map was generated based on data obtained from retrieved articles. In our study, a total of 4,852 publications launched before August 31, 2023 were accessed through the Web of Science Core Collection (WoSCC) database via our searching strategy. Significant fluctuations in global publications were observed in the field of MSCs in CVDs. China emerged as the nation with the largest number of publications, yet a shortage of high-quality articles was noted. The interplay among countries, institutions, journals and authors is visually represented in the enclosed figures. Importantly, current research trends and hotspots are elucidated. Cluster analysis on references has highlighted the considerable interest in exosomes, extracellular vesicles, and microvesicles. Besides, keywords analysis revealed a strong emphasis on myocardial infarction, therapy, and transplantation. Treatment methods-related keywords were prominent, while keywords associated with extracellular vesicles gathered significant attention from the long-term perspective. MSCs in CVDs have become a topic of active research interest, showcasing its latent value and potential. By summarizing the latest progress, identifying the research hotspots, and discussing the future trends in the advancement of MSCs in CVDs, we aim to offer valuable insights for considering research prospects.

Quercetin and dasatinib, two powerful senolytics in age-related cardiovascular disease.

Cellular senescence is characteristic of the development and progression of multiple age-associated diseases. Accumulation of senescent cells in the heart contributes to various age-related pathologies. Several compounds called senolytics have been designed to eliminate these cells within the tissues. In recent years, the use and study of senolytics increased, representing a promising field for finding accessible and safe therapies for cardiovascular disease (CVD) treatment. This mini-review discusses the changes in the aging heart and the participation of senescent cells in CVD, as well as the use of senolytics to prevent the progression of myocardial damage, mainly the effect of dasatinib and quercetin. In particular, the mechanisms and physiological effects of senolytics therapies in the aged heart are discussed.

Inflammation and blood cells in cardiovascular diseases

Coronary artery disease (CAD) is still the most important cause of death in developed societies. Atherosclerosis is recognized as a systemic immune inflammatory disease. Inflammation in CAD can be both local and systemic. The main advantage of hematological parameters and indices is that they are relatively inexpensive and therefore common and easy to find in daily clinical practice. In this review, we will try to explain the main hematological parameters and their effects on pathophysiology in patients with atherosclerotic cardiovascular disease.

The role of myeloid-derived immunosuppressive cells in cardiovascular disease.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population found in the bone marrow, peripheral blood, and tumor tissue. Their role is mainly to inhibit the monitoring function of innate and adaptive immune cells, which leads to the escape of tumor cells and promotes tumor development and metastasis. Moreover, recent studies have found that MDSCs are therapeutic in several autoimmune disorders due to their strong immunosuppressive ability. Additionally, studies have found that MDSCs have an important role in the formation and progression of other cardiovascular diseases, such as atherosclerosis, acute coronary syndrome, and hypertension. In this review, we will discuss the role of MDSCs in the pathogenesis and treatment of cardiovascular disease.

Long non-coding RNAs: The growth controller of vascular smooth muscle cells in cardiovascular diseases.

The active proliferation and migration of vascular smooth muscle cells supports the healing of vessel damage while their abnormal aggression or destitution contribute to the aberrant intima-medial structure and function in various cardiovascular diseases, so the understanding of the proliferation disorders of vascular smooth muscle cell and the related mechanism is the basis of effective intervention and control for cardiovascular diseases. Recently, long non-coding RNAs have stood out as upstream switchers for multiple proliferative signaling pathways and molecules, and many of them have been shown to conduce to the dysregulated proliferation and apoptosis of vascular smooth muscle cells under various pathogenic stimuli. This article discusses the long non-coding RNAs disclosed and linked to atherosclerosis, pulmonary hypertension, and aneurysms, and focuses upon their modulation of vascular smooth muscle cell population affecting three deadly cardiovascular diseases.

The role of γδ T17 cells in cardiovascular disease.

Due to the ability of γδ T cells to bridge adaptive and innate immunity, γδ T cells can respond to a variety of molecular cues and acquire the ability to induce a variety of cytokines such as IL-17 family, IFN-γ, IL-4, and IL-10. IL-17+ γδ T cells (γδ T17 cells) populations have recently received considerable interest as they are the major early source of IL-17A in many immune response models. However, the exact mechanism of γδ T17 cells is still poorly understood, especially in the context of cardiovascular disease (CVD). CVD is the leading cause of death in the world, and it tends to be younger. Here, we offer a review of the cardiovascular inflammatory and immune functions of γδ T17 cells in order to understand their role in CVD, which may be the key to developing new clinical applications.

Heartbreakers or Healers? Innate Lymphoid Cells in Cardiovascular Disease and Obesity.

Cardiovascular diseases (CVDs) are responsible for most pre-mature deaths worldwide, contributing significantly to the global burden of disease and its associated costs to individuals and healthcare systems. Obesity and associated metabolic inflammation underlie development of several major health conditions which act as direct risk factors for development of CVDs. Immune system responses contribute greatly to CVD development and progression, as well as disease resolution. Innate lymphoid cells (ILCs) are a family of helper-like and cytotoxic lymphocytes, typically enriched at barrier sites such as the skin, lung, and gastrointestinal tract. However, recent studies indicate that most solid organs and tissues are home to resident populations of ILCs - including those of the cardiovascular system. Despite their relative rarity, ILCs contribute to many important biological effects during health, whilst promoting inflammatory responses during tissue damage and disease. This mini review will discuss the evidence for pathological and protective roles of ILCs in CVD, and its associated risk factor, obesity.

Analysis of Immune and Inflammation Characteristics of Atherosclerosis from Different Sample Sources.

Background Atherosclerosis is the predominant cause of cardiovascular diseases. Existing studies suggest that the development of atherosclerosis is closely related to inflammation and immunity, but whether there are differences and similarities between atherosclerosis occurring at different sites is still unknown. We elucidated the pathological characteristics of peripheral vascular diseases by using bioinformatic analyses on immune cells and inflammation-related gene expression in atherosclerotic arteries and plaques. Methods Eight data sets regarding atherosclerosis were downloaded from the Gene Expression Omnibus database. Human immune genes were obtained from the IMMPORT website. The samples were scored and divided into high- and low-immune groups. Then the samples were analysed using weighted gene co-expression network analysis, while the modules were analysed using functional enrichment. The protein–protein interaction network was constructed using the STRING and Cytoscape databases. The hub immune genes were screened, and the correlation between hub immune genes and immune cells was analysed. Results Immune cells and their functions were significantly different during atherosclerosis development. The infiltration proportion of immune cells was approximately similar in samples from different sources of patients with carotid atherosclerosis. However, the sensitivity of lower extremity atherosclerosis samples to immune cells is lower than that of carotid atherosclerosis samples.The samples from the plaque and artery were mainly infiltrated by macrophages, T cells and mast cells. After immune cells were assessed, resting NK cells, activated mast cells and M0 macrophages were found to be key immune cells in atherosclerosis and plaque formation. In addition, CCL4, TLR2, IL1B and PTPRC were considered to be immune marker genes in atherosclerosis development. Conclusion. Bioinformatic data analysis confirms the essential role of immune cells in cardiovascular diseases, and also indicates some differences of immune and inflammation characteristics of atherosclerosis between carotid and lower extremity arteries.

Circular RNAs: regulators of vascular smooth muscle cells in cardiovascular diseases.

The aberrant expansion and dysfunction of vascular smooth muscle cells (VSMCs) contribute to the occurrence and development of many cardiovascular diseases. Circular RNAs, a new class of non-coding RNAs with the 3' and 5' ends covalently linked together due to back-splicing, have recently been revealed to function as new regulators of VSMCs. These circular RNAs mainly act as RNA sponge to downregulate other regulatory non-coding RNAs such as microRNAs, influencing the overgrowth and transformation of VSMCs under pathogenic conditions. The purpose of this review is to summarize how circular RNAs fluctuate their own expression in response to multiple stimuli in vitro and in vivo and how they modulate the phenotypic adaptation, proliferation, migration, apoptosis, and senescence of VSMCs, which in turn affects the progression of cardiovascular diseases. Finally, we highlight the potential of circular RNAs as the biomarkers and therapeutic targets for abnormal VSMCs and cardiovascular diseases.

The role of the mineralocorticoid receptor in immune cells in cardiovascular disease.

Chronic low-grade inflammation and immune cell activation are important mechanisms in the pathophysiology of cardiovascular disease (CVD). Therefore, targeted immunosuppression is a promising novel therapy to reduce cardiovascular risk. In this review, we identify the mineralocorticoid receptor (MR) on immune cells as a potential target to modulate inflammation. The MR is present in almost all cells of the cardiovascular system, including immune cells. Activation of the MRs in innate and adaptive immune cells induces inflammation which can contribute to CVD, by inducing endothelial dysfunction and hypertension. Moreover, it accelerates atherosclerotic plaque formation and destabilization and impairs tissue regeneration after ischaemic events. Identifying the molecular targets for these non-renal actions of the MR provides promising novel cardiovascular drug targets for mineralocorticoid receptor antagonists (MRAs), which are currently mainly applied in hypertension and heart failure. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

Liver damage promotes pro-inflammatory T-cell responses against apolipoprotein B-100.

Liver-derived apolipoprotein B-100 (ApoB100) is an autoantigen that is recognized by atherogenic CD4+ Tcells in cardiovascular disease (CVD). CVD is a major mortality risk for patients with chronic inflammatory liver diseases. However, the impact of liver damage for ApoB100-specific T-cell responses is unknown. We identified ApoB100-specific Tcells in blood from healthy controls, nonalcoholic fatty liver disease (NAFLD) patients, and CVD patients by activation-induced marker expression and analyzed their differentiation pattern in correlation to the lipid profile and liver damage parameters in a cross-sectional study. To assess the induction of extrahepatic ApoB100-specific Tcells upon transient liver damage in vivo, we performed hydrodynamic tail vein injections with diphtheria toxin A (DTA)-encoding plasmid in human ApoB100-transgenic mice. Utilizing immunodominant ApoB100-derived peptides, we found increased ApoB100-specific T-cell populations in NAFLD and CVD patients compared to healthy controls. In a peptide-specific manner, ApoB100 reactivity in healthy controls was accompanied by expression of the regulatory T (Treg)-cell transcription factor FOXP3. In contrast, FOXP3 expression decreased, whereas expression of pro-inflammatory cytokine interleukin (IL)-17A increased in ApoB100-specific Tcells from NAFLD and CVD patients. Dyslipidemia and liver damage parameters in blood correlated with reduced FOXP3 expression and elevated IL-17A production in ApoB100-specific T-cell populations, respectively. Moreover, DTA-mediated transient liver damage in human ApoB100-transgenic mice accumulated IL-17a-expressing ApoB100-specific Tcells in the periphery. Our results show that liver damage promotes pro-inflammatory ApoB100-specific T-cell populations, thereby providing a cellular mechanism for the increased CVD risk in liver disease patients.

Lymphatic Clearance of Immune Cells in Cardiovascular Disease.

Recent advances in our understanding of the lymphatic system, its function, development, and role in pathophysiology have changed our views on its importance. Historically thought to be solely involved in the transport of tissue fluid, lipids, and immune cells, the lymphatic system displays great heterogeneity and plasticity and is actively involved in immune cell regulation. Interference in any of these processes can be deleterious, both at the developmental and adult level. Preclinical studies into the cardiac lymphatic system have shown that invoking lymphangiogenesis and enhancing immune cell trafficking in ischaemic hearts can reduce myocardial oedema, reduce inflammation, and improve cardiac outcome. Understanding how immune cells and the lymphatic endothelium interact is also vital to understanding how the lymphatic vascular network can be manipulated to improve immune cell clearance. In this Review, we examine the different types of immune cells involved in fibrotic repair following myocardial infarction. We also discuss the development and function of the cardiac lymphatic vasculature and how some immune cells interact with the lymphatic endothelium in the heart. Finally, we establish how promoting lymphangiogenesis is now a prime therapeutic target for reducing immune cell persistence, inflammation, and oedema to restore heart function in ischaemic heart disease.

Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis.

Clonal hematopoiesis is a prevalent age-associated condition that results from the accumulation of somatic mutations in hematopoietic stem and progenitor cells (HSPCs). Mutations in driver genes, that confer cellular fitness, can lead to the development of expanding HSPC clones that increasingly give rise to progeny leukocytes harboring the somatic mutation. Because clonal hematopoiesis has been associated with heart disease, stroke, and mortality, the development of experimental systems that model these processes is key to understanding the mechanisms that underly this new risk factor. Bone marrow transplantation procedures involving myeloablative conditioning in mice, such as total-body irradiation (TBI), are commonly employed to study the role of immune cells in cardiovascular diseases. However, simultaneous damage to the bone marrow niche and other sites of interest, such as the heart and brain, is unavoidable with these procedures. Thus, our lab has developed two alternative methods to minimize or avoid possible side effects caused by TBI: 1) bone marrow transplantation with irradiation shielding and 2) adoptive BMT to non-conditioned mice. In shielded organs, the local environment is preserved allowing for the analysis of clonal hematopoiesis while the function of resident immune cells is unperturbed. In contrast, the adoptive BMT to non-conditioned mice has the additional advantage that both the local environments of the organs and the hematopoietic niche are preserved. Here, we compare three different hematopoietic cell reconstitution approaches and discuss their strengths and limitations for studies of clonal hematopoiesis in cardiovascular disease.

Mapping current research and identifying hotspots on mesenchymal stem cells in cardiovascular disease

BackgroundMesenchymal stem cells (MSCs) have important research value and broad application prospects in the cardiovascular disease. This study provides information on the latest progress, evolutionary path, frontier research hotspots, and future research developmental trends in this field.MethodsA knowledge map was generated by CiteSpace and VOSviewer analysis software based on data obtained from the literature on MSCs in the cardiovascular field.ResultsThe USA and China ranked at the top in terms of the percentage of articles, accounting for 34.306% and 28.550%, respectively. The institution with the highest number of research publications in this field was the University of Miami, followed by the Chinese Academy of Medical Sciences and Harvard University. The research institution with the highest ACI value was Harvard University, followed by the Mayo Clinic and the University of Cincinnati.The top three subjects in terms of the number of published articles were cell biology, cardiovascular system cardiology, and research experimental medicine. The journal with the most publications in this field was Circulation Research, followed by Scientific Reports and Biomaterials. The direction of research on MSCs in the cardiovascular system was divided into four parts: (1) tissue engineering, scaffolds, and extracellular matrix research; (2) cell transplantation, differentiation, proliferation, and signal transduction pathway research; (3) assessment of the efficacy of stem cells from different sources and administration methods in the treatment of acute myocardial infarction, myocardial hypertrophy, and heart failure; and (4) exosomes and extracellular vesicles research. Tissue research is the hotspot and frontier in this field.ConclusionMSC research has presented a gradual upward trend in the cardiovascular field. Multidisciplinary intersection is a characteristic of this field. Engineering and materials disciplines are particularly valued and have received attention from researchers. The progress in multidisciplinary research will provide motivation and technical support for the development of this field.

Cells in Cardiovascular Disease: Using Diversity to Confront Adversity

The present Special Issue on "Cells in Cardiovascular Disease" wants to offer a general overview of current cardiovascular research and illustrate how advances in the molecular characterization at the cellular level are providing unique insights into pathologies of the circulatory system [...].

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug.

Emodin is a natural occurring anthraquinone derivative isolated from roots and barks of numerous plants, molds, and lichens. It is found to be an active ingredient in different Chinese herbs including Rheum palmatum and Polygonam multiflorum, and it is a pleiotropic molecule with diuretic, vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory, and anti-cancer effects. Moreover, emodin has also been shown to have a wide activity of anti-cardiovascular diseases. It is mainly involved in multiple molecular targets such as inflammatory, anti-apoptosis, anti-hypertrophy, anti-fibrosis, anti-oxidative damage, abnormal, and excessive proliferation of smooth muscle cells in cardiovascular diseases. As a new type of cardiovascular disease treatment drug, emodin has broad application prospects. However, a large amount of evidences detailing the effect of emodin on many signaling pathways and cellular functions in cardiovascular disease, the overall understanding of its mechanisms of action remains elusive. In addition, by describing the evidence of the effects of emodin in detail, the toxicity and poor oral bioavailability of mice have been continuously discovered. This review aims to describe a timely overview of emodin related to the treatment of cardiovascular disease. The emphasis is to summarize the pharmacological effects of emodin as an anti-cardiovascular drug, as well as the targets and its potential mechanisms. Furthermore, the treatment of emodin compared with conventional cardiovascular drugs or target inhibitors, the toxicity, pharmacokinetics and derivatives of emodin were discussed.