Quantification of Sympathetic Nerve Traffic to the Heart: Electrophysiological Recording of Cardiac Sympathetic Nerve Activity in a Rodent Model.

The accurate measurement of sympathetic nerve activity is essential for advancing knowledge related to the mechanisms that underpin sympathetic activation in diseased states, such as acute heart failure. Considering sympathetic outflow throughout the body is differentially modulated, the most reliable method of measuring sympathetic traffic to individual organs is by way of direct electrophysiological recording of nerve activity. However, the surgical approach of accessing, exposing, and isolating the sympathetic nerve of interest is technically demanding, especially in the small size of a standard laboratory rat, one of the most common models for measuring SNA.

Role of noncoding RNAs in cardiac ageing.

The global population is estimated to reach 9.8 billion by 2050, of which 2.1 billion will comprise individuals above 60 years of age.

Therapeutic knockdown of miR-320 improves deteriorated cardiac function in a pre-clinical model of non-ischemic diabetic heart disease.

Non-ischemic diabetic heart disease (NiDHD) is characterized by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. Accelerated apoptotic cell death because of alteration of molecular signaling pathways due to dysregulation in microRNAs (miRNAs) plays a significant role in the development of NiDHD. Here, we aimed to determine the pathological role of cardiomyocyte-enriched pro-apoptotic miR-320 in the development of NiDHD.

Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart.

Pericytes (PCs) are abundant yet remain the most enigmatic and ill-defined cell population in the heart. Here, we investigated whether PCs can be reprogrammed to aid neovascularization. Primary PCs from human and mouse hearts acquired cytoskeletal proteins typical of vascular smooth muscle cells (VSMCs) upon exclusion of EGF/bFGF, which signal through ERK1/2, or upon exposure to the MEK inhibitor PD0325901.

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models.

The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat.

Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity.

Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to angiotensin 1-7 the latter having cardioprotective and vasorelaxation effects.

Increased neuronal activation in sympathoregulatory regions of the brain and spinal cord in type 2 diabetic rats.

Increased cardiac sympathetic nerve activity in type 2 diabetes mellitus (DM) suggests impaired autonomic control of the heart. However, the central regions that contribute to the autonomic cardiac pathologies in type 2 DM are unknown. Therefore, we tested the hypothesis that neuronal activation would be increased in central sympathoregulatory areas in a pre-clinical type 2 DM animal model.

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Background: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (MAChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism.

Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography.

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated ventricular afterload. We hypothesized that the mechanical stress on the RV associated with increased afterload impairs vasodilator function of the right coronary artery (RCA) in PH. Coronary vascular response was assessed using microangiography with synchrotron radiation (SR) in two well-established PH rat models, monocrotaline injection or the combined exposure to chronic hypoxia and vascular endothelial growth factor receptor blockade with Su5416 (SuHx model).

Publisher Correction: Dysregulation of ghrelin in diabetes impairs the vascular reparative response to hindlimb ischemia in a mouse model; clinical relevance to peripheral artery disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ghrelin and vascular protection.

Ghrelin is a small peptide with important roles in the regulation of appetite, gut motility, glucose homeostasis as well as cardiovascular protection. This review highlights the role that acyl ghrelin plays in maintaining normal endothelial function by maintaining the balance of vasodilator-vasoconstrictor factors, inhibiting inflammatory cytokine production and immune cell recruitment to sites of vascular injury and by promoting angiogenesis.

Exercise Regulates MicroRNAs to Preserve Coronary and Cardiac Function in the Diabetic Heart.

Rationale: Diabetic heart disease (DHD) is a debilitating manifestation of type 2 diabetes mellitus. Exercise has been proposed as a potential therapy for DHD, although the effectiveness of exercise in preventing or reversing the progression of DHD remains controversial. Cardiac function is critically dependent on the preservation of coronary vascular function.

Dysregulation of ghrelin in diabetes impairs the vascular reparative response to hindlimb ischemia in a mouse model; clinical relevance to peripheral artery disease.

Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD.

Acute myocardial infarction activates magnocellular vasopressin and oxytocin neurones.

Myocardial infarction (MI) is a leading cause of death worldwide. For those who survive the acute insult, the progressive dilation of the ventricle associated with chronic heart failure is driven by an adverse increase in circulating levels of the antidiuretic hormone, vasopressin, which is secreted from hypothalamic supraoptic (SON) and paraventricular nuclei (PVN) nerve terminals. Although increased vasopressin neuronal activity has been demonstrated in the latter stages of chronic heart failure, we hypothesised that vasopressin neurones become activated immediately following an acute MI.

Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model.

Coronary microvessel endothelial dysfunction and nitric oxide (NO) depletion contribute to elevated passive tension of cardiomyocytes, diastolic dysfunction and predispose the heart to heart failure with preserved ejection fraction. We examined if diastolic dysfunction at the level of the cardiomyocytes precedes coronary endothelial dysfunction in prediabetes. Further, we determined if myofilaments other than titin contribute to impairment.

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension.

Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously shown that IL-1 receptor antagonist (IL-1Ra) protects against murine BPD; therefore, we hypothesized that IL-1Ra may also be effective against BPD-PH. We employed daily injections of IL-1Ra in a murine model in which BPD/BPD-PH was induced by antenatal LPS and postnatal hyperoxia of 65% O.

Activation of oxytocin neurons in the paraventricular nucleus drives cardiac sympathetic nerve activation following myocardial infarction in rats.

Myocardial infarction (MI) initiates an increase in cardiac sympathetic nerve activity (SNA) that facilitates potentially fatal arrhythmias. The mechanism(s) underpinning sympathetic activation remain unclear. Some neuronal populations within the hypothalamic paraventricular nucleus (PVN) have been implicated in SNA.

Progressive Decrease in Coronary Vascular Function Associated With Type 2 Diabetic Heart Disease.

The causal factors underpinning the onset and progression of diabetic heart disease (DHD) remain to be fully elucidated. Myocardial function is critically dependent on optimal coronary blood flow. Considering vascular disease occurs early in diabetes due to endothelial dysfunction, this study aimed to determine whether impaired coronary perfusion contributes to the origins of myocardial dysfunction in DHD, or whether coronary and cardiac dysfunction are independent pathologies associated with diabetes.

Assessing the role of hypothalamic microglia and blood vessel disruption in the development of angiotensin II-dependent hypertension in Cyp1a1-Ren2 rats.

Elevated plasma levels of the hormone vasopressin have been implicated in the pathogenesis of some forms of hypertension. Hypothalamic paraventricular and supraoptic nuclei neurons regulate vasopressin secretion into the circulation. Vasopressin neuron activity is elevated by day 7 in the development of angiotensin II-dependent hypertension in Cyp1a1-Ren2 rats.

Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option.

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease. It is characterized by chronic pain at rest, skin ulcerations, and gangrene tissue loss. CLI is a highly morbid condition, resulting in a severely diminished quality of life and a significant risk of mortality.

Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels Following β-Adrenergic Receptor Blockade.

Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). Whereas β-adrenergic receptor (β-AR) blockers are routinely used for the management of MI, they may also counter β-AR-mediated vasodilation of coronary vessels. We have reported that ghrelin prevents sympathetic activation following MI.

Widespread Coronary Dysfunction in the Absence of HDL Receptor SR-B1 in an Ischemic Cardiomyopathy Mouse Model.

Reduced clearance of lipoproteins by HDL scavenger receptor class B1 (SR-B1) plays an important role in occlusive coronary artery disease. However, it is not clear how much microvascular dysfunction contributes to ischemic cardiomyopathy. Our aim was to determine the distribution of vascular dysfunction in vivo in the coronary circulation of male mice after brief exposure to Paigen high fat diet, and whether this vasomotor dysfunction involved nitric oxide (NO) and or endothelium derived hyperpolarization factors (EDHF).

A switch from GABA inhibition to excitation of vasopressin neurons exacerbates the development angiotensin II-dependent hypertension.

Hypothalamic magnocellular neurons secrete vasopressin into the systemic circulation to maintain blood pressure by increasing renal water reabsorption and by vasoconstriction. When blood pressure rises, baroreflex activation normally inhibits vasopressin neurons via activation of GABAergic inputs. However, plasma vasopressin levels are paradoxically elevated in several models of hypertension and in some patients with essential hypertension, despite increased blood pressure.

Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways.

Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction.