Search

Platelet derived growth factor B (PDGFB) / PDGFRβ signalling is a key regulator of the cardiovascular system in development, health, and disease. During angiogenesis PDGFB regulates pericyte migration and proliferation during development and in tissue repair. Pericytes confer vessel stability, maintain vessel integrity, and control vascular tone. In the field of regenerative medicine, pericytes have also risen to prominence as they were discovered to be the in-situ counterpart of mesenchymal stem/stromal cells (MSCs). Pdgfbret/ret mutantmice are pericyte-deficient. The PDGFB retention motif is deleted, reducing PDGFB retention in the pericellular space and extracellular matrix and therefore pericyte recruitment during angiogenesis. This reduction in vascular pericyte coverage in pdgfbret/ret mice manifests in phenotypic differences compared with pdgfb+/+ and pdgfbret/+ littermates. Of relevance, is the reported development of vascular associated brain calcification in 4–12-month-old pdgfbret/ret mice and alterations to left ventricular structure from 10 to 20 weeks of age. In this thesis, I have investigated the hypothesis that calcification develops throughout the vasculature in pdgfbret/ret mice and that alteration of left ventricular structure leads to a progressive decline in heart function. I also hypothesised that disruption to PDGFB/PDGFRβ signalling in vivo influences the in vitro properties of MSCs. To address my hypotheses, I used a combination of cardiovascular imaging techniques, positron emission tomography/computed tomography (PET/CT) and high-resolution cardiac ultrasound, alongside in vitro MSC osteogenic assays. Contrary to my original hypothesis, results of PET/CT imaging using 18F-NaF, a radioactive tracer with the propensity to bind to hydroxyapatite calcification, did not reveal any areas of ectopic calcification out with the brain in male or female pdgfbret/ret mice. No significant calcification was observed in the aortic arch, the descending thoracic aorta, heart, or kidneys. Indeed, calcification was restricted to the brain at 12 months of age and completely absent from pdgfb+/+ and pdgbret/+ littermates. However, I did observe that the extent and anatomical location of brain calcification was variable in pdgfbret/ret mice. Using high resolution cardiac ultrasound, I next evaluated the cardiac phenotype exhibited in male and female pdgfbret/ret mice over the course of 12 months. The results of this study reveal that both male and female pdgfbret/ret mice exhibit signs of cardiac dilation with increasing left ventricular end diastolic area at 3 months of age, whereas females exhibit an increase in left ventricular mass that may be the result of hypertrophic remodelling or oedema. However, over the course of 6, 9 and 12 months, this phenotype resolves in both male and female pdgfbret/ret mice and normal contractile function is maintained. Further analysis of cardiac structure and function was performed using speckle tracking echocardiography (STE) in a combined male and female cohort of pdgfb+/+, pdgfbret/+ and pdgfbret/ret mice. Using STE, subtle changes to segmental systolic and diastolic cardiac strain were detected at 9 and 12 months of age in pdgfbret/ret mice. These changes may preclude the onset of deterioration of cardiac function in pdgfbret/ret mice and requires further investigation beyond 12 months of age to conclude. Finally, I examined the effects of the pdgfbret mutation on the osteogenic potential of MSCs derived from large coronary vessels and various vascularised tissues including the kidney, the skeletal muscle, and the heart in vitro. Quantification of osteogenic potential saw an increase in calcium deposition in combined pdgfbret MSC tissues. Tissue specific osteogenic potential was highly variable although there was a trend towards an increased osteogenesis in pdgfbret mutant tissues. Together, data from my studies indicate that pdgfbret/ret mice exhibit a transient cardiac phenotype which is ameliorated and have variable levels of calcification exclusive to the brain at 12 months of age. This data also indicates that MSCs derived from pdgfbret mutants have greater osteogenic potential although the tissue specificity of this potential requires further investigation.

Heart failure is characterized by the heart losing its capacity to pump sufficient blood to match the body’s demand. It is caused by a variety of cardiovascular impairments. Among them, atherosclerosis is the most common one. Although, a variety of medicines selectively target this pathology, the death rate due to atherosclerosis associated heart disorders remain high. To address this issue, the use of antioxidants combined with conventional therapy to achieve synergistic effects has gained popularity. Melatonin is one of such antioxidants. In addition to its potent antioxidant activity, this molecule acts in harmony to protect the cardiovascular tissue. This review explores the various mechanisms by which melatonin protects the cardiovascular tissue. This information will contribute further insights into the role of melatonin in maintaining cardiovascular homeostasis in normal as well as in pathological conditions. It will also help us to better understand the potential synergistic effects of melatonin with conventional therapy to successfully target the heart failure associated with atherosclerosis.

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element–binding protein in regulating fructose metabolism.

The semipermeable capillary walls not only enable the removal of excess body water and solutes during hemodialysis (HD) but also provide an essential mechanism for maintaining cardiovascular homeostasis. Here, we investigated transcapillary transport processes on the whole-body level using the three-pore model of the capillary endothelium with large, small and ultrasmall pores. The transcapillary transport and cardiovascular response to a 4-h hemodialysis (HD) with 2 L ultrafiltration were analyzed by simulations in a virtual patient using the three-pore model of the capillary wall integrated in the whole-body compartmental model of the cardiovascular system with baroreflex mechanisms. The three-pore model revealed substantial changes during HD in the magnitude and direction of transcapillary water flows through small and ultrasmall pores and associated changes in the transcapillary convective transport of proteins and small solutes. The fraction of total capillary hydraulic conductivity attributed to ultrasmall pores was found to play an important role in the transcapillary water transport during HD thus influencing the cardiovascular response to HD. The presented model provides a novel computational framework for a detailed analysis of microvascular exchange during HD and as such may contribute to a better understanding of dialysis-induced changes in blood volume and blood pressure.

Despite the long history of the concept where infection plays a significant role in cardiovascular diseases (atherosclerosis in particular), today it is relevant and represented a significant interest.This article discusses H. pylori role in mechanisms of cardiovascular homeostasis disturbance. H. pylori involvement in atherogenic damage of arteries, and/or plaque destabilization is no doubt. This vidence is detailed in this review article.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in the cardiovascular system, clinical applications centered on NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process, based on computational modeling and flow-mediated dilation, to assess endothelial function and vulnerability of atherosclerotic plaque. Then, emerging bioimaging technologies that have the potential to experimentally measure arterial NO concentration were discussed, including Raman spectroscopy and electrochemical sensors. In addition to diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the NO release platform to treat endothelial dysfunction and atherosclerosis and inhaled NO therapy to treat pulmonary hypertension and COVID-19. Two potential methods to improve the effectiveness of existing NO therapy were also discussed, including the combination of NO release platform and computational modeling, and stem cell therapy, which currently remains at the laboratory stage but has clinical potential for the treatment of CVD.

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.

MiRNA-regulated processes are pivotal in cardiovascular homeostasis and disease. These short non-coding RNAs have ideal properties that could be utilized as potential biomarkers; moreover, their functions as post-transcriptional regulators of mRNA make them interesting therapeutic targets. In this review, we summarize the current state of miRNA-based biomarkers in a variety of diseases leading to heart failure, as well as provide an outlook on developing miRNA-based therapies in the heart failure field.

Background: L-Arginine is an amino acid which is involved in nitric oxide production regulating vascular tone and cardiovascular homeostasis. Hypertension is one of the most common comorbidities worldwide, and leads to endothelial dysfunction contributing to atherosclerosis, inflammation, and oxidative stress. Frailty is a syndrome of decreased physiological reserves with increased susceptibility to stressors leading to higher mortality, hospitalization, disability, and functional and cognitive impairment. Cognitive impairment is a very common feature in hypertensive frail older adults. Hence, it is very important to treat cognitive impairment to delay and/or prevent adverse events. Our study, thus, investigated the effects of 4-weeks supplementation of L-Arginine on global cognitive function. Methods: We studied 101 frail older patients from April 2020 to April 2021. All subjects were recruited from ASL (local health company of Italian Ministry of Health) Avellino, Italy. All patients fulfilled all of the following inclusion criteria: a previous diagnosis of hypertension, a confirmed frail status, age >65 years. The exclusion criteria were: age Results: We are reporting here the results in 52 patients who hitherto successfully completed the study. The cognitive screening was available at baseline (before treatment) and during a follow-up of 4 weeks. The non-treated group (n=27) had a Montreal Cognitive Assessment (MoCA) score 22.9±0.9 at basal and 23.4±1.0 at follow-up (p=0.06). The treated group (oral L-Arginine, 1.66 g, twice a day; n=25) displayed a MoCA score 23.1±0.7 at basal and 24.2±0.6 at follow-up (p Conclusions: Our data show a significant improvement in the MoCA score in the group treated with L-Arginine. More extensive studies are needed to verify the efficacy of L-Arginine in this population.

The effects of the apelinergic system components apelin (AP) and elabela (ELA) in the regulation of human cardiovascular homeostasis, and data concerning the relationship between ELA and AP and coronary artery disease (CAD) are yet unknown. The aim of the study was the evaluation of AP, ELA and APJ-receptor levels in the plasma of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS). The study group consisted of 114 patients with CAD and 33 healthy controls. Patients were divided into two groups: with CCS (n = 30) and ACS (n = 84). Routine laboratory tests and plasma ELA, AP-17, AP-13 and APJ receptor levels were measured. Echocardiographic data were analyzed in all patients. Levels of AP-17 and ELA were significantly lower in CCS than in healthy controls and ACS patients. We demonstrated significant increase of levels of plasma apelinergic system peptides, especially ELA and AP-17 in ACS patients compared with healthy controls and CCS, suggestive of compensating up-regulation mechanisms. There is a relationship between circulating ELA and AP-17 levels and classical, biochemical markers of ischemia and left ventricular ejection faction as well.

Fluctuation analysis in intervals between heartbeats provides important indices related to autonomic modulation of heart rate variability (HRV). These indices are considered predictors of morbidity and mortality as they are frequently altered in patients with chronic degenerative diseases, especially in those with cardiovascular and metabolic diseases. Similarly, a reduction in HRV is common with aging. In all cases, cardiovascular fitness is often reduced to below the predicted values. In turn, increases in cardiovascular fitness through regular physical exercise, especially aerobic exercise, represent an important therapeutic tool capable of promoting positive adjustments in cardiac autonomic modulation. These adjustments are characterized by reduced sympathetic modulatory influence and/or increased vagal modulatory influence on the heart, increasing the HRV. Therefore, several methodological tools have been used to assess the degree of impairment of autonomic modulation and the therapeutic effects of physical exercise. In contrast, establishment of strict protocols in experimental design is a main challenge in establishing HRV analysis as a robust parameter for evaluating cardiovascular homeostasis. Thus, this review aimed to contribute to the understanding of autonomic modulation of HRV and its relationship with cardiovascular fitness, highlighting the advances made thus far, the applicability of analysis tools, and the confounding factors observed frequently.

Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes’ performance and recovery.

Vasopressin is involved in cardiovascular homeostasis that can influence coronary perfusion. It is commonly used as a local vasoconstricting agent during gynaecological procedures. We present a case of cardiac arrest and inverse Takotsubo features following intramyometrial vasopressin administration during myomectomy. The patient was successfully resuscitated and recovered completely. Cardiac presentation was compatible with inverse Takotsubo cardiomyopathy that could have been triggered by high-dose vasopressin-induced coronary vasoconstriction. The patient's cardiac function resolved with no long-term sequelae. Takotsubo cardiomyopathy usually results from an excessive catecholaminergic surge. High-dose vasopressin-induced coronary vasospasm could have been the mechanism underlying the clinical presentation in our patient. Learning points Local vasopressin administration during gynaecological procedures can result in rare but severe cardiovascular compromise.Takotsubo cardiomyopathy can result from multiple rare causes.High-dose vasopressin may cause Takotsubo cardiomyopathy features via coronary vasoconstriction.

Highlights • Exercise training is beneficial to the cardiovascular system. • Autophagy is critical in maintaining cardiovascular homeostasis and function. • Excessive or insufficient autophagy or autophagic flux can lead to cardiovascular disease. • Exercise-mediated bidirectional regulation of autophagy can prevent cardiovascular diseases., Cardiovascular disease is the leading cause of human death worldwide. Autophagy is an evolutionarily conserved degradation pathway, which is a highly conserved cellular degradation process in which lysosomes decompose their own organelles and recycle the resulting macromolecules. Autophagy is critical in maintaining cardiovascular homeostasis and function, and excessive or insufficient autophagy or autophagic flux can lead to cardiovascular disease. Enormous evidence indicates that exercise training plays a beneficial role in the prevention and treatment of cardiovascular diseases. The regulation of autophagy during exercise is a bidirectional process. For cardiovascular disease caused by either insufficient or excessive autophagy, exercise training restores normal autophagy function and delays the progression of cardiovascular disease. An in-depth exploration and discussion of exercise-mediated regulation of autophagy in the cardiovascular system can broaden our view about the prevention of various autophagy-related diseases through exercise training. In this article, we review autophagy and its related signaling pathways, as well as autophagy-dependent beneficial effects of exercise in cardiovascular system., Graphical abstract Image, graphical abstract

Purpose: Endoglin is a transmembrane glycoprotein which plays an important role in maintaining cardiovascular homeostasis. One of its forms, soluble endoglin (sEng), a molecule with antiangiogenic properties, has been found overexpressed in patients suffering from hypercholesterolemia, diabetes mellitus and hypertension, and is proposed as a marker of endothelial damage. Accordingly, we aimed to quantify the efficacy of various antihypertensive regimens on sEng levels, in hypertensive patients with endothelial dysfunction. Patients and methods: 323 patients were enrolled, and there were 99 patients with normal blood pressure values, 106 hypertensive patients under chronic treatment with different types of antihypertensive molecules (beta blockers, calcium channel blockers, and diuretics) in monotherapy, and 118 hypertensive patients under chronic treatment with perindopril. sEng plasma levels were quantified and were correlated with classical methods of assessing the endothelial damage. Results: Patients under chronic treatment with perindopril had lower sEng plasma levels compared with the other group of hypertensive patients under different regimens of antihypertensive treatment (sEng: 4.73±1.39 versus 5.63±2.33, p

Endothelial NOS (eNOS), and its product NO, are vital components of the control of vasomotor function and cardiovascular homeostasis. In the present review, we will take a deep dive into eNOS enzymology, function and mechanisms regulating endothelial NO. The mechanisms regulating eNOS and NO synthesis discussed here include alterations to transcriptional, post-translational modifications and protein-protein regulations. Also, we will discuss the phenotypes associated with various eNOS mutants and the consequences of a disrupted eNOS/NO cascade, highlighting the importance of eNOS function and vascular homeostasis. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.

© 2018, Canadian Science Publishing. All rights reserved. The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain’s higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the “cortical autonomic network” (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

The cardiovascular system can be programmed by a diversity of early-life insults, leading to cardiovascular disease (CVD) in adulthood. This notion is now termed developmental origins of health and disease (DOHaD). Emerging evidence indicates hydrogen sulfide (H2S), a crucial regulator of cardiovascular homeostasis, plays a pathogenetic role in CVD of developmental origins. Conversely, early H2S-based interventions have proved beneficial in preventing adult-onset CVD in animal studies via reversing programming processes by so-called reprogramming. The focus of this review will first summarize the current knowledge on H2S implicated in cardiovascular programming. This will be followed by supporting evidence for the links between H2S signaling and underlying mechanisms of cardiovascular programming, such as oxidative stress, nitric oxide deficiency, dysregulated nutrient-sensing signals, activation of the renin–angiotensin system, and gut microbiota dysbiosis. It will also provide an overview from animal models regarding how H2S-based reprogramming interventions, such as precursors of H2S and H2S donors, may prevent CVD of developmental origins. A better understanding of cardiovascular programming and recent advances in H2S-based interventions might provide the answers to bring down the global burden of CVD.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

Maintenance of normal function of mitochondria is vital to the fate and health of cardiomyocytes. Mitochondrial quality control (MQC) mechanisms are essential in governing mitochondrial integrity and function. The ubiquitin-proteasome system (UPS), mitochondrial dynamics, and mitophagy are three major components of MQC. With the progress of research, our understanding of MQC mechanisms continues to deepen. Gradually, we realize that the three MQC mechanisms are not independent of each other. To the contrary, there are crosstalk among the mechanisms, which can make them interact with each other and cooperate well, forming a triangle interplay. Briefly, the UPS system can regulate the level of mitochondrial dynamic proteins and mitophagy receptors. In the process of Parkin-dependent mitophagy, the UPS is also widely activated, performing critical roles. Mitochondrial dynamics have a profound influence on mitophagy. In this review, we provide new processes of the three major MQC mechanisms in the background of cardiomyocytes and delve into the relationship between them.

The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin–angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein–coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.

Cardiovascular diseases (CVDs) are the result of complex pathophysiological processes in the tissues comprising the heart and blood vessels. Inflammation is the main culprit for the development of cardiovascular dysfunction, and it may be traced to cellular stress events including apoptosis, oxidative and shear stress, and cellular and humoral immune responses, all of which impair the system's structure and function. An intracellular chaperone, heat shock protein 60 (HSP60) is an intriguing example of a protein that may both be an ally and a foe for cardiovascular homeostasis; on one hand providing protection against cellular injury, and on the other triggering damaging responses through innate and adaptive immunity. In this review we will discuss the functions of HSP60 and its effects on cells and the immune system regulation, only to later address its implications in the development and progression of CVD. Lastly, we summarize the outcome of various studies targeting HSP60 as a potential therapeutic strategy for cardiovascular and other diseases.

The baroreceptor reflex is a powerful neural feedback that regulates arterial pressure (AP). Mechanosensitive channels transduce pulsatile AP to electrical signals in baroreceptors. Here we show that tentonin 3 (TTN3/TMEM150C), a cation channel activated by mechanical strokes, is essential for detecting AP changes in the aortic arch. TTN3 was expressed in nerve terminals in the aortic arch and nodose ganglion (NG) neurons. Genetic ablation of Ttn3 induced ambient hypertension, tachycardia, AP fluctuations, and impaired baroreflex sensitivity. Chemogenetic silencing or activation of Ttn3+ neurons in the NG resulted in an increase in AP and heart rate, or vice versa. More important, overexpression of Ttn3 in the NG of Ttn3-/- mice reversed the cardiovascular changes observed in Ttn3-/- mice. We conclude that TTN3 is a molecular component contributing to the sensing of dynamic AP changes in baroreceptors.

Summary The vasculature is innervated by a network of peripheral afferents that sense and regulate blood flow. Here, we describe a system of non-peptidergic sensory neurons with cell bodies in the spinal ganglia that regulate vascular tone in the distal arteries. We identify a population of mechanosensitive neurons, marked by tropomyosin receptor kinase C (TrkC) and tyrosine hydroxylase in the dorsal root ganglia, which projects to blood vessels. Local stimulation of TrkC neurons decreases vessel diameter and blood flow, whereas systemic activation increases systolic blood pressure and heart rate variability via the sympathetic nervous system. Ablation of the neurons provokes variability in local blood flow, leading to a reduction in systolic blood pressure, increased heart rate variability, and ultimately lethality within 48 h. Thus, a population of TrkC+ sensory neurons forms part of a sensory-feedback mechanism that maintains cardiovascular homeostasis through the autonomic nervous system., Graphical abstract, Highlights • TrkC+/Th+ DRG neurons project to blood vessels • Local stimulation of TrkC+ DRG neurons decreases vessel diameter and blood flow • Systemic activation of TrkC+ DRG neurons increases blood pressure and heart rate • Ablation of TrkC+ neurons dysregulates cardiovascular homeostasis and is lethal, Morelli et al. identify a subpopulation of peripheral sensory neurons marked by TrkC and Th that projects to distal blood vessels. They demonstrate that these neurons regulate peripheral perfusion, blood pressure, and heart rate.

11 p., Heart rate (HR) and blood pressure (BP) autonomic modulation and baroreflex sensitivity (BRS) are important indexes of cardiovascular homeostasis. However, methodological errors are often observed, such as joint analysis of men and women. Another important aspect is that we still do not know whether cardiorespiratory fitness influences these autonomic parameters in healthy individuals. OBJECTIVES: This study aimed to investigate whether sex can affect BRS, autonomic modulation of HR and BP variabilities (HRV and BPV, respectively), as well as the influence of cardiorespiratory fitness on these autonomic parameters. METHODS: Healthy men and women (N=120) were assigned to groups according to the peak oxygen consumption (VO2 peak) obtained in the cardiorespiratory test: low cardiorespiratory fitness (VO2 peak: 22-38 ml/kg/min), moderate cardiorespiratory fitness (VO2 peak: 38-48 ml/kg/min), and high cardiorespiratory fitness (VO2 peak>48 ml/kg/min). HRV and BPV evaluations were performed for all groups in the frequency domain by spectral analysis. Spontaneous BRS was assessed using the sequence method. RESULTS: Women presented lower BP values compared with men. HR did not differ between sexes, but showed an inverse relationship with cardiorespiratory performance. The HRV analysis showed greater sympathetic modulation for men and greater vagal modulation for women. Men and women presented similar results for systolic BPV and BRS, and cardiorespiratory performance did not influence any of the autonomic parameters evaluated. CONCLUSION: Cardiorespiratory fitness does not interfere with HRV and BPV autonomic modulation or BRS. However, the cardiac modulatory balance differs between sexes, with a greater influence of the autonomic vagal component in women and the sympathetic component in men.

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.

Cardiac muscle develops more force when it is activated at longer lengths. The concentration of Ca(2+) required to develop half-maximal force also decreases. These effects are known as length-dependent activation and are thought to play critical roles in the Frank-Starling relationship and cardiovascular homeostasis. The molecular mechanisms underpinning length-dependent activation remain unclear, but recent experiments suggest that they may include recruitment of myosin heads from the off (sometimes called super-relaxed) state. This manuscript presents a mathematical model of muscle contraction that was developed to investigate this hypothesis. Myosin heads in the model transitioned between an off state (that could not interact with actin), an on state (that could bind to actin), and a single attached state. Simulations were fitted to experimental data using multidimensional parameter optimization. Statistical analysis showed that a model in which the rate of the off-to-on transition increased linearly with force reproduced the length-dependent behavior of chemically permeabilized myocardium better than a model with a constant off-to-on transition rate (F-test, p < 0.001). This result suggests that the thick-filament transitions are modulated by force. Additional calculations showed that the model incorporating a mechanosensitive thick filament could also reproduce twitch responses measured in a trabecula stretched to different lengths. A final set of simulations was then used to test the model. These calculations predicted how reducing passive stiffness would impact the length dependence of the calcium sensitivity of contractile force. The prediction (a 60% reduction in ΔpCa(50)) mimicked the 58% reduction in ΔpCa(50) in myocardium from rats that expressed a giant isoform of titin and had low resting tension. Together, these computational results suggest that force-dependent recruitment of myosin heads from the thick-filament off state contributes to length-dependent activation and the Frank-Starling relationship.

Background The Golden Ratio (GR), derived from the Fibonacci sequences, has multiple representations in nature, as expressions of the repetition of specific geometric shapes called fractals. Methods The aim of the study focused on investigation of the cardiovascular homeostasis, at rest and during effort testing, with determination of the validity of the GR at the level of variables extracted from serial ECG. We used a group of 230 young subjects (average age 19.21 ± 1.87), each subject performing a 6 min submaximal exercise ergometer test (Astrand & Rhyming Protocol). We were interested in estimate the ratio between the electrical diastole and electrical systole (TQ/QT) and between the cardiac cycle and electrical diastole (RR/TQ), which has been much discussed as being related to GR value. Results We proposed using a new synthetic fractal indicator (SFI), with dynamic nonlinear evolution and we determined the intervals of acceptability for SFI. The mean values of the SFI of our subjects were significantly close to GR value, aspect that suggests the presence of harmonic rhythm, under different conditions of existence and adaptation of the human organism (rest and submaximal effort). The SFI and the heart rate values had very strong correlations, at rest (R = 0.88, p Conclusions Our results show a fractal dimension of the ECG interval dynamics for the study group. The proposed SFI imposes itself as a relatively simple parameter for assessing heart’s electrical functionality during cardiac cycle that can be applied both at rest and exercise.

Background Medicinal plants or herbs produce a bounty of bioactive phytochemicals. These phytochemicals can influence a variety of physiological events related to cardiovascular health through multiple underlying mechanisms, such as their role as antioxidative, anti-ischemic, anti-proliferative, hypotensive, anti-thrombotic, and anti-hypercholesterolemic agents. Purpose The purpose of this review is to summarize and connect evidences supporting the use of phytotherapy in the management of some of the most common cardiovascular impairments, molecular mechanisms underlying cardio-protection mediated by herbs, and clinical studies which are positively linked with the use of herbs in cardiovascular biology. Additionally, we also describe several adverse effects associated with some of the herbal plants and their products to provide a balanced set of studies in favor or against phytotherapy in cardiovascular health that may help global discourses on this matter. Methods Studies relating to the use of medicinal plants were mined by strategically searching scientific databases including Google Scholar, PubMed and Science Direct. Investigations involving approximately 175 articles including reviews, research articles, meta-analyses, and cross-sectional and observational studies were retrieved and analyzed in line with the stated purpose of this study. Results A positive correlation between the use of medicinal plants and cardiovascular health was observed. While maintaining cardiovascular physiology, medicinal plants and their derivatives seem to govern a variety of cellular mechanisms involved in vasoconstriction and vasorelaxation, which in turn, are important aspects of cardiovascular homeostasis. Furthermore, a variety of studies including clinical trials, cross-sectional studies, and meta-analyses have also supported the anti-hypertensive and thus, cardio-protective effects, of medicinal plants. Apart from this, evidence is also available for the potential drawbacks of several herbs and their products indicating that the unsupervised use of many herbs may lead to severe health issues. Conclusions The cardio-protective outcomes of medicinal plants and their derivatives are supported by ever-increasing studies, while evidences exist for the potential drawbacks of some of the herbs. A balanced view about the use of medicinal plants and their derivative in cardiovascular biology thus needs to be outlined by researchers and the medical community. The novelty and exhaustiveness of the present manuscript is reflected by the detailed outline of the molecular basis of “herbal cardio-protection”, active involvement of several herbs in ameliorating the cardiovascular status, adverse effects of medicinal plants, and the clinical studies considering the use of phytotherapy, all on a single platform.

The gasotransmitter hydrogen sulfide (H2S) is an important tuner of the cardiovascular homeostasis, and its deficiency is etiologically associated with a number of cardiovascular diseases. Therefore, the research of original moieties able to release H2S represents a timely issue for drug discovery. In this work, we developed a collection of iminothioethers (ITEs), exhibiting H2S-releasing properties and producing vasorelaxing effects on rat aortic rings. Derivatives 4 and 11, selected as representative of slow and fast rate H2S donors, respectively, produced a complete recovery of the basal coronary flow, reverting the AngII-induced effects in isolated rat hearts. In addition, studies on human aortic smooth muscle cells (HASMCs) demonstrated membrane hyperpolarizing effects, well related to the intracellular generation of H2S. Taken together, the results obtained support ITEs 4 and 11 as new pharmacological tools, as well as effective and innovative H2S donors for cardiovascular drug discovery.

The effects of testosterone on cardiovascular homeostasis are still not well understood. The objective of this work was to evaluate the effects of testosterone in the absence or presence of inhibition of Aromatase (4-hydroxyandrostenedione) and/or 5α reductase (Finasteride) enzymatic activities on the myocardial remodeling 30 days after ischemia/reperfusion (I/R) injury in gonadectomized rats. Results showed that testosterone administration to ORX rats resulted in decreased myocardial damaged area, inflammatory infiltrates and reduced MMP-3 and 13 expressions. Interestingly, Finasteride administration resulted in a greater decrease in scar tissue, inflammatory infiltrates, along with a significant decrease in MMP-3 and 13 expressions. In contrast, 4-hydroxyandrostenedione administrations increased all parameters. Our results suggest that testosterone does not have a direct effect since simultaneous inhibition of aromatase and 5α-reductase did not induce significant changes in I/R induced myocardial injury., Summary: Coronary ischemia/reperfusion-induced injury in gonadectomyzed male rats is decreased by testosterone, protection is increased by blocking its 5α-reduction and blocked by inhibition of its aromatization.

Vasopressin is a unique hormone with complex receptor physiology and numerous physiologic functions beyond its well-known vascular actions and osmoregulation. While vasopressin has in the past been primarily used in the management of diabetes insipidus and acute gastrointestinal bleeding, an increased understanding of the physiology of refractory shock, and the role of vasopressin in maintaining cardiovascular homeostasis prompted a renewed interest in the therapeutic roles for this hormone in the critical care setting. Identifying vasopressin-deficient individuals for the purposes of assessing responsiveness to exogenous hormone and prognosticating outcome has expanded research into the evaluation of vasopressin and its precursor, copeptin as useful biomarkers. This review summarizes the current evidence for vasopressin in critically ill children, with a specific focus on its use in the management of shock. We outline important considerations and current guidelines, when considering the use of vasopressin or its analogues in the pediatric critical care setting.

Through the success of basic and disease-specific research, cancer survivors are one of the largest growing subsets of individuals accessing the healthcare system. Interestingly, cardiovascular disease is the second leading cause of morbidity and mortality in cancer survivors after recurrent malignancy. This recognition has helped stimulate a collaboration between oncology and cardiology practitioners and researchers, and the portmanteau cardio-oncology (also known as onco-cardiology) can now be found in many medical centers. This collaboration promises new insights into how cancer therapies impact cardiovascular homeostasis and long-term effects on cancer survivors. In this review, we will discuss the most recent views on the cardiotoxicity related to various classes of chemotherapy agents and radiation. We will also discuss broadly the current strategies for treating and preventing cardiovascular effects of cancer therapy.