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1.
Am J Physiol Cell Physiol ; 322(2): C218-C230, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1673516

ABSTRACT

Selective autophagy of mitochondria, known as mitophagy, is a major quality control pathway in the heart that is involved in removing unwanted or dysfunctional mitochondria from the cell. Baseline mitophagy is critical for maintaining fitness of the mitochondrial network by continuous turnover of aged and less-functional mitochondria. Mitophagy is also critical in adapting to stress associated with mitochondrial damage or dysfunction. The removal of damaged mitochondria prevents reactive oxygen species-mediated damage to proteins and DNA and suppresses activation of inflammation and cell death. Impairments in mitophagy are associated with the pathogenesis of many diseases, including cancers, inflammatory diseases, neurodegeneration, and cardiovascular disease. Mitophagy is a highly regulated and complex process that requires the coordination of labeling dysfunctional mitochondria for degradation while simultaneously promoting de novo autophagosome biogenesis adjacent to the cargo. In this review, we provide an update on our current understanding of these steps in mitophagy induction and discuss the physiological and pathophysiological consequences of altered mitophagy in the heart.


Subject(s)
COVID-19/metabolism , Cardiovascular Diseases/metabolism , Cardiovascular System/metabolism , Mitochondria/metabolism , Mitophagy/physiology , Reactive Oxygen Species/metabolism , Animals , COVID-19/pathology , Cardiovascular Diseases/pathology , Cardiovascular System/pathology , Humans , Mitochondria/pathology , Phagocytosis/physiology
2.
Ann N Y Acad Sci ; 1507(1): 70-83, 2022 01.
Article in English | MEDLINE | ID: covidwho-1673249

ABSTRACT

For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.


Subject(s)
Aging/genetics , Aging/metabolism , Congresses as Topic/trends , Longevity/physiology , Research Report , Autophagy/physiology , COVID-19/genetics , COVID-19/metabolism , COVID-19/mortality , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/therapy , Humans , Metabolomics/methods , Metabolomics/trends , Nervous System Diseases/genetics , Nervous System Diseases/metabolism , Nervous System Diseases/therapy , Stem Cell Transplantation/methods , Stem Cell Transplantation/trends
3.
Int J Mol Sci ; 22(16)2021 Aug 23.
Article in English | MEDLINE | ID: covidwho-1662696

ABSTRACT

Magnesium (Mg) is a pivotal and very complex component of healthy aging in the cardiovascular-muscle-bone triad. Low Mg levels and low Mg intake are common in the general aging population and are associated with poorer outcomes than higher levels, including vascular calcification, endothelial dysfunction, osteoporosis, or muscle dysfunction/sarcopenia. While Mg supplementation appears to reverse these processes and benefit the triad, more randomized clinical trials are needed. These will allow improvement of preventive and curative strategies and propose guidelines regarding the pharmaceutical forms and the dosages and durations of treatment in order to optimize and adapt Mg prescription for healthy aging and for older vulnerable persons with comorbidities.


Subject(s)
Cardiovascular Diseases/metabolism , Magnesium/metabolism , Osteoporosis/metabolism , Sarcopenia/metabolism , Aging/metabolism , Animals , Bone and Bones/metabolism , Healthy Aging/metabolism , Humans , Muscle Strength/physiology , Muscle, Skeletal/metabolism
4.
Int J Mol Sci ; 23(2)2022 Jan 15.
Article in English | MEDLINE | ID: covidwho-1631216

ABSTRACT

Angiotensin II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) are G-protein-coupled receptors (GPCRs) expressed on the surface of a great variety of cells: immune cells, vascular smooth cells, endothelial cells, and fibroblasts express ETAR and AT1R, which are activated by endothelin 1 (ET1) and angiotensin II (AngII), respectively. Certain autoantibodies are specific for these receptors and can regulate their function, thus being known as functional autoantibodies. The function of these antibodies is similar to that of natural ligands, and it involves not only vasoconstriction, but also the secretion of proinflammatory cytokines (such as interleukin-6 (IL6), IL8 and TNF-α), collagen production by fibroblasts, and reactive oxygen species (ROS) release by fibroblasts and neutrophils. The role of autoantibodies against AT1R and ETAR (AT1R-AAs and ETAR-AAs, respectively) is well described in the pathogenesis of many medical conditions (e.g., systemic sclerosis (SSc) and SSc-associated pulmonary hypertension, cystic fibrosis, and allograft dysfunction), but their implications in cardiovascular diseases are still unclear. This review summarizes the current evidence regarding the effects of AT1R-AAs and ETAR-AAs in cardiovascular pathologies, highlighting their roles in heart transplantation and mechanical circulatory support, preeclampsia, and acute coronary syndromes.


Subject(s)
Autoantibodies/metabolism , Cardiovascular Diseases/immunology , Receptor, Angiotensin, Type 1/immunology , Receptor, Endothelin A/immunology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Collagen/metabolism , Humans , Interleukin-6/metabolism , Interleukin-8/metabolism , Reactive Oxygen Species/metabolism , Receptor, Angiotensin, Type 1/metabolism , Tumor Necrosis Factor-alpha/metabolism
5.
Bull Exp Biol Med ; 172(3): 283-287, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1611428

ABSTRACT

We studied laboratory parameters of patients with COVID-19 against the background of chronic pathologies (cardiovascular pathologies, obesity, type 2 diabetes melitus, and cardiovascular pathologies with allergy to statins). A decrease in pH and a shift in the electrolyte balance of blood plasma were revealed in all studied groups and were most pronounced in patients with cardiovascular pathologies with allergy to statin. It was found that low pH promotes destruction of lipid components of the erythrocyte membranes in patients with chronic pathologies, which was seen from a decrease in Na+/K+-ATPase activity and significant hyponatrenemia. In patients with cardiovascular pathologies and allergy to statins, erythrocyte membranes were most sensitive to a decrease in pH, while erythrocyte membranes of obese patients showed the greatest resistance to low pH and oxidative stress.


Subject(s)
COVID-19/complications , Hyponatremia/etiology , Hypoxia/complications , Sodium-Potassium-Exchanging ATPase/physiology , Aged , COVID-19/metabolism , Cardiovascular Diseases/complications , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/virology , Case-Control Studies , Chronic Disease , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/virology , Drug Hypersensitivity/complications , Drug Hypersensitivity/metabolism , Drug Hypersensitivity/virology , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Female , Fluid Shifts/physiology , Humans , Hydrogen-Ion Concentration , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hyponatremia/metabolism , Hyponatremia/virology , Hypoxia/metabolism , Lipid Peroxidation/physiology , Male , Middle Aged , Obesity/complications , Obesity/metabolism , Obesity/virology , Oxidative Stress/physiology , SARS-CoV-2/physiology , Sodium/metabolism , Stress, Physiological/physiology
6.
Biomolecules ; 12(1)2021 12 24.
Article in English | MEDLINE | ID: covidwho-1581037

ABSTRACT

Coronavirus disease 2019 (COVID-19), the pandemic infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with an extremely heterogeneous spectrum of symptoms and signs. The clinical manifestations seem to be correlated with disease severity. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality compared to women. Such variability can be ascribed to both sex-related biological factors and gender-related behavioral cues. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Cardiovascular diseases play a central role in determining COVID-19 outcome, whether they are pre-existent or arose upon infection. We will pay particular attention to the impact of sex and gender on cardiovascular manifestations related to COVID-19. Finally, we will discuss the sex-dependent variability in some biomarkers for the evaluation of COVID-19 infection and prognosis. The aim of this work is to highlight the significance of gendered medicine in setting up personalized programs for COVID-19 prevention, clinical evaluation and treatment.


Subject(s)
COVID-19 , Cardiovascular Diseases , Pandemics , SARS-CoV-2/metabolism , Sex Characteristics , COVID-19/complications , COVID-19/epidemiology , COVID-19/metabolism , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Female , Humans , Male , Risk Factors , Severity of Illness Index , Sex Factors
7.
Int J Mol Sci ; 22(24)2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1580692

ABSTRACT

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.


Subject(s)
COVID-19/complications , Heart Failure/metabolism , Heart/virology , Animals , Blood/virology , Blood Physiological Phenomena/immunology , COVID-19/physiopathology , Cardiomegaly/metabolism , Cardiovascular Diseases/metabolism , Cardiovascular Physiological Phenomena/immunology , Disease Models, Animal , Endothelium/metabolism , Heart/physiopathology , Heart Failure/virology , Hydroxychloroquine/pharmacology , Male , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , Muscle Cells/metabolism , Myocardium/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Ventricular Remodeling/physiology
8.
Biomed Res Int ; 2021: 7073348, 2021.
Article in English | MEDLINE | ID: covidwho-1560583

ABSTRACT

Coronavirus disease 2019 (COVID-19) may lead to acute respiratory disease; cardiovascular, gastrointestinal, and coagulation complications; and even death. One of the major complications is cardiovascular disorders, including arrhythmias, myocarditis, pericarditis, and acute coronary artery disease. The aim of this study was to evaluate the frequency of cardiovascular complications and to determine its association with the prognosis of COVID-19 patients. In a prospective analytic study, 137 hospitalized COVID-19 patients were enrolled. During hospitalization, an electrocardiogram (ECG) was performed every other day, and laboratory tests such as cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were done 0, 6, and 12 hours after admission. These tests were repeated for patients with chest pain or ECG changes. Patients were categorized into three groups (improved, complicated, and expired patients) and assessed for the rate and type of arrhythmias, cardiac complications, lab tests, and outcomes of treatments. There was no significant relationship among the three groups related to primary arrhythmia and arrhythmias during treatment. The most common arrhythmia during hospitalization and after treatment was ST-T fragment changes. There was a significant age difference between the three groups (P = 0.001). There was a significant difference among the three groups for some underlying diseases, including diabetes mellitus (P = 0.003) and hyperlipidemia (P = 0.004). In our study, different types of arrhythmias had no association with patients' outcomes but age over 60 years, diabetes mellitus, and hyperlipidemia played an important role in the prognosis of COVID-19 cases.


Subject(s)
COVID-19/complications , COVID-19/pathology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/pathology , Adult , Aged , Blood Coagulation/physiology , COVID-19/metabolism , Cardiovascular Diseases/metabolism , Creatine Kinase/metabolism , Electrocardiography/methods , Female , Heart/physiopathology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Troponin I/metabolism , Young Adult
9.
Curr Probl Dermatol ; 55: 329-338, 2021.
Article in English | MEDLINE | ID: covidwho-1541964

ABSTRACT

While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.


Subject(s)
Cardiovascular Diseases/prevention & control , Skin Neoplasms/epidemiology , Skin/radiation effects , Ultraviolet Rays , Vitamin D/biosynthesis , Cardiovascular Diseases/metabolism , Humans , Metabolic Networks and Pathways/radiation effects , Risk Assessment , Skin/metabolism , Skin/pathology , Skin Neoplasms/etiology , Skin Neoplasms/pathology , Skin Neoplasms/prevention & control
10.
Pharmacol Res ; 169: 105689, 2021 07.
Article in English | MEDLINE | ID: covidwho-1525917

ABSTRACT

Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is an apoB100 containing lipoprotein covalently bound to apolipoprotein(a) [apo(a)], a glycoprotein. Plasma Lp(a) levels are to a large extent determined by genetics. Its link to cardiovascular disease (CVD) may be driven by its pro-inflammatory effects, of which its association with oxidized phospholipids (oxPL) bound to Lp(a) is the most studied. Various inflammatory conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus, acquired immunodeficiency syndrome, and chronic renal failure are associated with high Lp(a) levels. In cases of RA, high Lp(a) levels are reversed by interleukin-6 receptor (IL-6R) blockade by tocilizumab, suggesting a potential role for IL-6 in regulating Lp(a) plasma levels. Elevated levels of IL-6 and IL-6R polymorphisms are associated with CVD. Therapies aimed at lowering apo(a) and thereby reducing plasma Lp(a) levels are in clinical trials. Their results will determine if reductions in apo(a) and Lp(a) decrease cardiovascular outcomes. As we enter this new arena of available treatments, there is a need to improve our understanding of mechanisms. This review will focus on the role of Lp(a) in inflammation and CVD.


Subject(s)
Inflammation/metabolism , Lipoprotein(a)/blood , Animals , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Humans , Inflammation/blood , Inflammation/etiology , Lipoprotein(a)/metabolism , Lipoprotein(a)/physiology
11.
Int J Mol Sci ; 22(22)2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1524023

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...].


Subject(s)
COVID-19/pathology , Cardiovascular Diseases/complications , Diabetes Complications/pathology , COVID-19/complications , COVID-19/virology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Humans , Lipoproteins, LDL/metabolism , SARS-CoV-2/isolation & purification
12.
Molecules ; 26(22)2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1512512

ABSTRACT

The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Phytochemicals/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Humans , Phytochemicals/chemistry , Phytochemicals/metabolism , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Plants, Medicinal/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
13.
Int J Mol Sci ; 22(21)2021 Oct 28.
Article in English | MEDLINE | ID: covidwho-1512376

ABSTRACT

Cardiovascular diseases are currently among the leading causes of morbidity and mortality in many developed countries. They are distinguished by chronic and latent development, a course with stages of worsening of symptoms and a period of improvement, and a constant potential threat to life. One of the most important disorders in cardiovascular disease is ischemic stroke. The causes of ischemic stroke can be divided into non-modifiable and modifiable causes. One treatment modality from a neurological point of view is acetylsalicylic acid (ASA), which blocks cyclooxygenase and, thus, thromboxane synthesis. The legitimacy of its administration does not raise any doubts in the case of the acute phase of stroke in patients in whom thrombolytic treatment cannot be initiated. The measurement of thromboxane B2 (TxB2) in serum (a stable metabolic product of TxA2) is the only test that measures the effect of aspirin on the activity of COX-1 in platelets. Measurement of thromboxane B2 may be a potential biomarker of vascular disease risk in patients treated with aspirin. The aim of this study is to present the role of thromboxane B2 in ischemic stroke and to present effective therapies for the treatment of ischemic stroke. Scientific articles from the PubMed database were used for the work, which were selected on the basis of a search for "thromboxane and stroke". Subsequently, a restriction was introduced for works older than 10 years, those concerning animals, and those without full text access. Ultimately, 58 articles were selected. It was shown that a high concentration of TXB2 may be a risk factor for ischemic stroke or ischemic heart disease. However, there is insufficient evidence to suggest that thromboxane could be used in clinical practice as a marker of ischemic stroke. The inclusion of ASA in the prevention of stroke has a beneficial effect that is associated with the effect on thromboxane. However, its insufficient power in 25% or even 50% of the population should be taken into account. An alternative and/or additional therapy could be a selective antagonist of the thromboxane receptor. Thromboxane A2 production is inhibited by estrogen; therefore, the risk of CVD after the menopause and among men is higher. More research is needed in this area.


Subject(s)
Ischemic Stroke/metabolism , Thromboxane B2/metabolism , Animals , Aspirin/therapeutic use , Cardiovascular Diseases/blood , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke/blood , Ischemic Stroke/drug therapy , Ischemic Stroke/physiopathology , Thromboxane B2/blood
14.
Int J Mol Sci ; 22(20)2021 Oct 19.
Article in English | MEDLINE | ID: covidwho-1477961

ABSTRACT

Chronic diseases and viral infections have threatened human life over the ages and constitute the main reason for increasing death globally. The rising burden of these diseases extends to negatively affecting the economy and trading globally, as well as daily life, which requires inexpensive, novel, and safe therapeutics. Therefore, scientists have paid close attention to probiotics as safe remedies to combat these morbidities owing to their health benefits and biotherapeutic effects. Probiotics have been broadly adopted as functional foods, nutraceuticals, and food supplements to improve human health and prevent some morbidity. Intriguingly, recent research indicates that probiotics are a promising solution for treating and prophylactic against certain dangerous diseases. Probiotics could also be associated with their essential role in animating the immune system to fight COVID-19 infection. This comprehensive review concentrates on the newest literature on probiotics and their metabolism in treating life-threatening diseases, including immune disorders, pathogens, inflammatory and allergic diseases, cancer, cardiovascular disease, gastrointestinal dysfunctions, and COVID-19 infection. The recent information in this report will particularly furnish a platform for emerging novel probiotics-based therapeutics as cheap and safe, encouraging researchers and stakeholders to develop innovative treatments based on probiotics to prevent and treat chronic and viral diseases.


Subject(s)
Chronic Disease/therapy , Probiotics/administration & dosage , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/therapy , Fatty Acids, Volatile/metabolism , Gastrointestinal Microbiome , Humans , Immune System/metabolism , Inflammation/metabolism , Inflammation/pathology , Neoplasms/metabolism , Neoplasms/therapy , Virus Diseases/immunology , Virus Diseases/metabolism , Virus Diseases/therapy
15.
Pharmacol Rev ; 73(3): 924-967, 2021 07.
Article in English | MEDLINE | ID: covidwho-1447969

ABSTRACT

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1ß monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.


Subject(s)
Atherosclerosis , COVID-19 , Cardiovascular Agents , Cardiovascular Diseases , Endothelium, Vascular , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , Atherosclerosis/physiopathology , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Agents/classification , Cardiovascular Agents/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Drug Discovery , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Humans , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , SARS-CoV-2
16.
Cardiovasc Hematol Disord Drug Targets ; 20(3): 181-184, 2020.
Article in English | MEDLINE | ID: covidwho-1435708

ABSTRACT

Nowadays Coronavirus Disease 2019 (Covid-19) is increasing mortality all over the world mercilessly. We are learning almost every day about its new symptoms and that it mutates quickly. This disease has tied us up and made us desperate. The death rate from this disease has increased in patients who had pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. Intravenous infusions of ACEIs and ARBs in experimental animals increase the number of ACE2 receptors. Therefore, it may be one of the reasons that COVID-19 infects the cells of patients treating hypertension. However, most of the congress of cardiology do not recommend to discontinue these anti-hypertensive drugs. Therefore, this brief report evaluates Covid-19 in the view of cardiovascular diseases taking into account current reports and suggests some possible solutions to keep the virus under control.


Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacokinetics , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Age Factors , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , Antihypertensive Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Cardiovascular Diseases/metabolism , Humans , Hypertension/drug therapy , Pandemics , SARS-CoV-2 , Severity of Illness Index , Thromboembolism/etiology , Thromboembolism/physiopathology
18.
Int J Mol Sci ; 22(15)2021 Jul 21.
Article in English | MEDLINE | ID: covidwho-1346495

ABSTRACT

Exosomes are nano-sized vesicles secreted by most cells that contain a variety of biological molecules, such as lipids, proteins and nucleic acids. They have been recognized as important mediators for long-distance cell-to-cell communication and are involved in a variety of biological processes. Exosomes have unique advantages, positioning them as highly effective drug delivery tools and providing a distinct means of delivering various therapeutic agents to target cells. In addition, as a new clinical diagnostic biomarker, exosomes play an important role in many aspects of human health and disease, including endocrinology, inflammation, cancer, and cardiovascular disease. In this review, we summarize the development of exosome-based drug delivery tools and the validation of novel biomarkers, and illustrate the role of exosomes as therapeutic targets in the prevention and treatment of various diseases.


Subject(s)
Biomarkers/metabolism , Cardiovascular Diseases/prevention & control , Drug Delivery Systems , Exosomes/metabolism , Inflammation/prevention & control , Neoplasms/prevention & control , Pharmaceutical Preparations/administration & dosage , Cardiovascular Diseases/metabolism , Humans , Inflammation/metabolism , Neoplasms/metabolism
19.
Cells ; 10(7)2021 07 13.
Article in English | MEDLINE | ID: covidwho-1314588

ABSTRACT

Transthyretin (TTR) is a tetrameric protein transporting hormones in the plasma and brain, which has many other activities that have not been fully acknowledged. TTR is a positive indicator of nutrition status and is negatively correlated with inflammation. TTR is a neuroprotective and oxidative-stress-suppressing factor. The TTR structure is destabilized by mutations, oxidative modifications, aging, proteolysis, and metal cations, including Ca2+. Destabilized TTR molecules form amyloid deposits, resulting in senile and familial amyloidopathies. This review links structural stability of TTR with the environmental factors, particularly oxidative stress and Ca2+, and the processes involved in the pathogenesis of TTR-related diseases. The roles of TTR in biomineralization, calcification, and osteoarticular and cardiovascular diseases are broadly discussed. The association of TTR-related diseases and vascular and ligament tissue calcification with TTR levels and TTR structure is presented. It is indicated that unaggregated TTR and TTR amyloid are bound by vicious cycles, and that TTR may have an as yet undetermined role(s) at the crossroads of calcification, blood coagulation, and immune response.


Subject(s)
Arthritis/metabolism , Cardiovascular Diseases/metabolism , Osteoporosis/metabolism , Prealbumin/metabolism , Amyloid/chemistry , Amyloid/metabolism , Amyloidosis/metabolism , Animals , Humans , Oxidative Stress , Prealbumin/chemistry , Protein Conformation , Protein Stability
20.
Viruses ; 13(7)2021 07 12.
Article in English | MEDLINE | ID: covidwho-1308454

ABSTRACT

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Cardiovascular Diseases/virology , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Blood Vessels/metabolism , Blood Vessels/pathology , Blood Vessels/virology , Cardiovascular Diseases/metabolism , Heart/virology , Humans , Pandemics
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