Review

Authors: Michael Roerecke

Alcohol consumption has been shown to have complex, and sometimes paradoxical, associations with cardiovascular diseases (CVDs). Several hundred epidemiological studies on this topic have been published in recent decades. In this narrative review, the epidemiological evidence will be examined for the associations between alcohol consumption, including average alcohol consumption, drinking patterns, and alcohol use disorders, and CVDs, including ischaemic heart disease, stroke, hypertension, atrial fibrillation, cardiomyopathy, and heart failure. Methodological shortcomings, such as exposure classification and measurement, reference groups, and confounding variables (measured or unmeasured) are discussed. Based on systematic reviews and meta-analyses, the evidence seems to indicate non-linear relationships with many CVDs. Large-scale longitudinal epidemiological studies with multiple detailed exposure and outcome measurements, and the extensive assessment of genetic and confounding variables, are necessary to elucidate these associations further. Conflicting associations depending on the exposure measurement and CVD outcome are hard to reconcile, and make clinical and public health recommendations difficult. Furthermore, the impact of alcohol on other health outcomes needs to be taken into account. For people who drink alcohol, the less alcohol consumed the better.

Topics: Alcohol Drinking; Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; Diagnosis, Differential; Disease Susceptibility; Ethanol; Health Impact Assessment; Humans; Risk Factors

PubMed: 34684419
DOI: 10.3390/nu13103419

Review

Authors: Brian J North, David A Sinclair

The average lifespan of humans is increasing, and with it the percentage of people entering the 65 and older age group is growing rapidly and will continue to do so in the next 20 years. Within this age group, cardiovascular disease will remain the leading cause of death, and the cost associated with treatment will continue to increase. Aging is an inevitable part of life and unfortunately poses the largest risk factor for cardiovascular disease. Although numerous studies in the cardiovascular field have considered both young and aged humans, there are still many unanswered questions as to how the genetic pathways that regulate aging in model organisms influence cardiovascular aging. Likewise, in the molecular biology of aging field, few studies fully assess the role of these aging pathways in cardiovascular health. Fortunately, this gap is beginning to close, and these two fields are merging together. We provide an overview of some of the key genes involved in regulating lifespan and health span, including sirtuins, AMP-activated protein kinase, mammalian target of rapamycin, and insulin-like growth factor 1 and their roles regulating cardiovascular health. We then discuss a series of review articles that will appear in succession and provide a more comprehensive analysis of studies carried out linking genes of aging and cardiovascular health, and perspectives of future directions of these two intimately linked fields.

Topics: Age Factors; Aged; Aging; Animals; Cardiovascular Diseases; Cardiovascular System; Gene Expression Regulation; Humans; Longevity; Prognosis; Risk Assessment; Risk Factors

PubMed: 22499900
DOI: 10.1161/CIRCRESAHA.111.246876

Review

Authors: Haitao Cui, Shida Miao, Timothy Esworthy...

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Compared to traditional therapeutic strategies, three-dimensional (3D) bioprinting is one of the most advanced techniques for creating complicated cardiovascular implants with biomimetic features, which are capable of recapitulating both the native physiochemical and biomechanical characteristics of the cardiovascular system. The present review provides an overview of the cardiovascular system, as well as describes the principles of, and recent advances in, 3D bioprinting cardiovascular tissues and models. Moreover, this review will focus on the applications of 3D bioprinting technology in cardiovascular repair/regeneration and pharmacological modeling, further discussing current challenges and perspectives.

Topics: Biomimetic Materials; Bioprinting; Cardiovascular System; Humans; Printing, Three-Dimensional; Regeneration; Tissue Engineering

PubMed: 30053441
DOI: 10.1016/j.addr.2018.07.014

Review

Authors: Maria Paz Ocaranza, Jaime A Riquelme, Lorena García...

The renin-angiotensin system is an important component of the cardiovascular system. Mounting evidence suggests that the metabolic products of angiotensin I and II - initially thought to be biologically inactive - have key roles in cardiovascular physiology and pathophysiology. This non-canonical axis of the renin-angiotensin system consists of angiotensin 1-7, angiotensin 1-9, angiotensin-converting enzyme 2, the type 2 angiotensin II receptor (ATR), the proto-oncogene Mas receptor and the Mas-related G protein-coupled receptor member D. Each of these components has been shown to counteract the effects of the classical renin-angiotensin system. This counter-regulatory renin-angiotensin system has a central role in the pathogenesis and development of various cardiovascular diseases and, therefore, represents a potential therapeutic target. In this Review, we provide the latest insights into the complexity and interplay of the components of the non-canonical renin-angiotensin system, and discuss the function and therapeutic potential of targeting this system to treat cardiovascular disease.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Humans; Molecular Targeted Therapy; Proto-Oncogene Mas; Renin-Angiotensin System

PubMed: 31427727
DOI: 10.1038/s41569-019-0244-8

Review

Authors: A A Knowlton, A R Lee

Estrogen is a potent steroid with pleiotropic effects, which have yet to be fully elucidated. Estrogen has both nuclear and non-nuclear effects. The rapid response to estrogen, which involves a membrane associated estrogen receptor(ER) and is protective, involves signaling through PI3K, Akt, and ERK 1/2. The nuclear response is much slower, as the ER-estrogen complex moves to the nucleus, where it functions as a transcription factor, both activating and repressing gene expression. Several different ERs regulate the specificity of response to estrogen, and appear to have specific effects in cardiac remodeling and the response to injury. However, much remains to be understood about the selectivity of these receptors and their specific effects on gene expression. Basic studies have demonstrated that estrogen treatment prevents apoptosis and necrosis of cardiac and endothelial cells. Estrogen also attenuates pathologic cardiac hypertrophy. Estrogen may have great benefit in aging as an anti-inflammatory agent. However, clinical investigations of estrogen have had mixed results, and not shown the clear-cut benefit of more basic investigations. This can be explained in part by differences in study design: in basic studies estrogen treatment was used immediately or shortly after ovariectomy, while in some key clinical trials, estrogen was given years after menopause. Further basic research into the underlying molecular mechanisms of estrogen's actions is essential to provide a better comprehension of the many properties of this powerful hormone.

Topics: Aging; Animals; Blood Vessels; Cardiovascular Diseases; Cardiovascular System; Estrogen Replacement Therapy; Estrogens; Humans; Inflammation; Menopause; Myocardium; Receptors, Estrogen; Signal Transduction

PubMed: 22484805
DOI: 10.1016/j.pharmthera.2012.03.007

Review

Authors: Sarah Costantino, Francesco Paneni, Francesco Cosentino...

Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart.

Topics: Aging; Animals; Cardiovascular Diseases; Cardiovascular System; Gene Expression Regulation, Developmental; Humans; Signal Transduction

PubMed: 26391109
DOI: 10.1113/JP270538

Review

Authors: Saeid Golbidi, Jefferson C Frisbee, Ismail Laher...

Psychological stresses are associated with cardiovascular diseases to the extent that cardiovascular diseases are among the most important group of psychosomatic diseases. The longstanding association between stress and cardiovascular disease exists despite a large ambiguity about the underlying mechanisms. An array of possibilities have been proposed including overactivity of the autonomic nervous system and humoral changes, which then converge on endothelial dysfunction that initiates unwanted cardiovascular consequences. We review some of the features of the two most important stress-activated systems, i.e., the humoral and nervous systems, and focus on alterations in endothelial function that could ensue as a result of these changes. Cardiac and hematologic consequences of stress are also addressed briefly. It is likely that activation of the inflammatory cascade in association with oxidative imbalance represents key pathophysiological components of stress-induced cardiovascular changes. We also review some of the commonly used animal models of stress and discuss the cardiovascular outcomes reported in these models of stress. The unique ability of animals for adaptation under stressful conditions lessens the extrapolation of laboratory findings to conditions of human stress. An animal model of unpredictable chronic stress, which applies various stress modules in a random fashion, might be a useful solution to this predicament. The use of stress markers as indicators of stress intensity is also discussed in various models of animal stress and in clinical studies.

Topics: Adaptation, Physiological; Adaptation, Psychological; Animals; Autonomic Nervous System; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Chronic Disease; Disease Models, Animal; Endothelium, Vascular; Humans; Risk Factors; Signal Transduction; Stress, Psychological

PubMed: 25888514
DOI: 10.1152/ajpheart.00859.2014

Review

Authors: Sreepadaarchana Munjuluri, Dru A Wilkerson, Gagandeep Sooch...

Capsaicin is a potent agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel and is a common component found in the fruits of the genus Capsicum plants, which have been known to humanity and consumed in food for approximately 7000-9000 years. The fruits of Capsicum plants, such as chili pepper, have been long recognized for their high nutritional value. Additionally, capsaicin itself has been proposed to exhibit vasodilatory, antimicrobial, anti-cancer, and antinociceptive properties. However, a growing body of evidence reveals a vasoconstrictory potential of capsaicin acting via the vascular TRPV1 channel and suggests that unnecessary high consumption of capsaicin may cause severe consequences, including vasospasm and myocardial infarction in people with underlying inflammatory conditions. This review focuses on vascular TRPV1 channels that are endogenously expressed in both vascular smooth muscle and endothelial cells and emphasizes the role of inflammation in sensitizing the TRPV1 channel to capsaicin activation. Tilting the balance between the beneficial vasodilatory action of capsaicin and its unwanted vasoconstrictive effects may precipitate adverse outcomes such as vasospasm and myocardial infarction, especially in the presence of proinflammatory mediators.

Topics: Animals; Blood Vessels; Capsaicin; Cardiovascular System; Humans; Inflammation; TRPV Cation Channels; Vasodilation

PubMed: 35011580
DOI: 10.3390/cells11010018

Review

Authors: Alice E Kane, David A Sinclair

The sirtuin family of nicotinamide adenine dinucleotide-dependent deacylases (SIRT1-7) are thought to be responsible, in large part, for the cardiometabolic benefits of lean diets and exercise and when upregulated can delay key aspects of aging. SIRT1, for example, protects against a decline in vascular endothelial function, metabolic syndrome, ischemia-reperfusion injury, obesity, and cardiomyopathy, and SIRT3 is protective against dyslipidemia and ischemia-reperfusion injury. With increasing age, however, nicotinamide adenine dinucleotide levels and sirtuin activity steadily decrease, and the decline is further exacerbated by obesity and sedentary lifestyles. Activation of sirtuins or nicotinamide adenine dinucleotide repletion induces angiogenesis, insulin sensitivity, and other health benefits in a wide range of age-related cardiovascular and metabolic disease models. Human clinical trials testing agents that activate SIRT1 or boost nicotinamide adenine dinucleotide levels are in progress and show promise in their ability to improve the health of cardiovascular and metabolic disease patients.

Topics: Age Factors; Aging; Animals; Cardiovascular Diseases; Cardiovascular System; Enzyme Activation; Enzyme Activators; Humans; Metabolic Diseases; NAD; Sirtuins; Up-Regulation

PubMed: 30355082
DOI: 10.1161/CIRCRESAHA.118.312498

Review

Authors: E Jozefczuk, T J Guzik, M Siedlinski...

Sphingosine-1-phosphate (S1P) is a signaling lipid, synthetized by sphingosine kinases (SPHK1 and SPHK2), that affects cardiovascular function in various ways. S1P signaling is complex, particularly since its molecular action is reliant on the differential expression of its receptors (S1PR1, S1PR2, S1PR3, S1PR4, S1PR5) within various tissues. Significance of this sphingolipid is manifested early in vertebrate development as certain defects in S1P signaling result in embryonic lethality due to defective vasculo- or cardiogenesis. Similar in the mature organism, S1P orchestrates both physiological and pathological processes occurring in the heart and vasculature of higher eukaryotes. S1P regulates cell fate, vascular tone, endothelial function and integrity as well as lymphocyte trafficking, thus disbalance in its production and signaling has been linked with development of such pathologies as arterial hypertension, atherosclerosis, endothelial dysfunction and aberrant angiogenesis. Number of signaling mechanisms are critical - from endothelial nitric oxide synthase through STAT3, MAPK and Akt pathways to HDL particles involved in redox and inflammatory balance. Moreover, S1P controls both acute cardiac responses (cardiac inotropy and chronotropy), as well as chronic processes (such as apoptosis and hypertrophy), hence numerous studies demonstrate significance of S1P in the pathogenesis of hypertrophic/fibrotic heart disease, myocardial infarction and heart failure. This review presents current knowledge concerning the role of S1P in the cardiovascular system, as well as potential therapeutic approaches to target S1P signaling in cardiovascular diseases.

Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Embryonic Development; Hemodynamics; Humans; Lysophospholipids; Neovascularization, Physiologic; Receptors, Lysosphingolipid; Signal Transduction; Sphingosine

PubMed: 32278039
DOI: 10.1016/j.phrs.2020.104793