Ying and Yang of Ceramide in the Vascular Endothelium.

Ceramides, a group of biologically active sphingolipids, have been described as the new cholesterol given strong evidence linking high plasma ceramide with endothelial damage, risk for early adverse cardiovascular events, and development of cardiometabolic disease. This relationship has sparked great interest in investigating therapeutic targets with the goal of suppressing ceramide formation. However, the growing data challenge this paradigm of ceramide as solely eliciting detrimental effects to the cardiovascular system.

Is the peripheral microcirculation a window into the human coronary microvasculature?

An increasing body of evidence suggests a pivotal role for the microvasculature in the development of cardiovascular disease. A dysfunctional coronary microvascular network, specifically within endothelial cells-the inner most cell layer of vessels-is considered a strong, independent risk factor for future major adverse cardiac events. However, challenges exist with evaluating this critical vascular bed, as many of the currently available techniques are highly invasive and cost prohibitive.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity.

Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis.

Background: Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis.

Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Addressing the decline in graduate students' mental well-being.

At the American Physiology Summit 2023 session entitled, "Mental Health for Graduate Students," numerous students expressed struggling with poor mental well-being primarily because of negative experiences during their graduate training. In fact, studies show that up to 50% of graduate students report symptoms of depression, anxiety, or burnout during their training, and poor mental well-being is a major contributor to students' decision to leave academia. Most of the current solutions focus on treatment or wellness strategies; while these are important and necessary, the training environment or culture that often contributes to worsening well-being continues to persist.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium.

Estrogen and the Vascular Endothelium: The Unanswered Questions.

Premenopausal women have a lower incidence of cardiovascular disease (CVD) compared with their age-matched male counterparts; however, this discrepancy is abolished following the transition to menopause or during low estrogen states. This, combined with a large amount of basic and preclinical data indicating that estrogen is vasculoprotective, supports the concept that hormone therapy could improve cardiovascular health. However, clinical outcomes in individuals undergoing estrogen treatment have been highly variable, challenging the current paradigm regarding the role of estrogen in the fight against heart disease.

17β-Estradiol promotes sex-specific dysfunction in isolated human arterioles.

Despite data showing that estrogen is vasculoprotective in large conduit arteries, hormone therapy (HT) during menopause has not proven to mitigate cardiovascular disease (CVD) risk. Estrogen exposure through prolonged oral contraceptive use and gender-affirming therapy can also increase cis- and trans-females' risk for future CVD, respectively. The microvasculature is a unique vascular bed that when dysfunctional can independently predict future adverse cardiac events; however, studies on the influence of estrogen on human microvessels are limited.

New developments in translational microcirculatory research.

Microvascular disease plays a critical role in systemic end-organ dysfunction, and treatment of microvascular pathologies may greatly reduce cardiovascular morbidity and mortality. The Call for Papers collection: New Developments in Translational Microcirculatory Research highlights key advances in our understanding of the role of microvessels in the development of chronic diseases as well as therapeutic strategies to enhance microvascular function. This Mini Review provides a concise summary of these advances and draws from other relevant research to provide the most up-to-date information on the influence of cutaneous, cerebrovascular, coronary, and peripheral microcirculation on the pathophysiology of obesity, hypertension, cardiovascular aging, peripheral artery disease, and cognitive impairment.

High-Dose IV Hydroxocobalamin (Vitamin B12) in Septic Shock: A Double-Blind, Allocation-Concealed, Placebo-Controlled Single-Center Pilot Randomized Controlled Trial (The Intravenous Hydroxocobalamin in Septic Shock Trial).

Background: Elevated hydrogen sulfide (HS) contributes to vasodilatation and hypotension in septic shock, and traditional therapies do not target this pathophysiologic mechanism. High-dose IV hydroxocobalamin scavenges and prevents HS formation, which may restore vascular tone and may accentuate recovery. No experimental human studies have tested high-dose IV hydroxocobalamin in adults with septic shock.

S1P (Sphingosine-1-Phosphate)-Induced Vasodilation in Human Resistance Arterioles During Health and Disease.

Background: Preclinical studies suggest that S1P (sphingosine-1-phosphate) influences blood pressure regulation primarily through NO-induced vasodilation. Because microvascular tone significantly contributes to mean arterial pressure, the mechanism of S1P on human resistance arterioles was investigated. We hypothesized that S1P induces NO-mediated vasodilation in human arterioles from adults without coronary artery disease (non-coronary artery disease) through activation of 2 receptors, S1PR (S1P receptor 1) and S1PR (S1P receptor 3).

Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases.

Introduction: Catecholamine-resistant vasoplegia is a potentially devastating complication during liver transplantation. Hydroxocobalamin has emerged as a treatment for vasoplegia associated with cardiac surgery, liver transplantation, and septic shock.

Presentation Of Case: We performed a retrospective review of patients who underwent liver transplantation between October 2015 and May 2020 to evaluate the efficiency of hydroxocobalamin in this setting.

Blockade of endothelial Mas receptor restores the vasomotor response to phenylephrine in human resistance arterioles pretreated with captopril and exposed to propofol.

Background: Hypotension that is resistant to phenylephrine is a complication that occurs in anesthetized patients treated with angiotensin converting enzyme (ACE) inhibitors. We tested the hypothesis that Ang 1-7 and the endothelial Mas receptor contribute to vasodilation produced by propofol in the presence of captopril.

Methods: The internal diameters of human adipose resistance arterioles were measured before and after administration of phenylephrine (10 to 10 M) in the presence and absence of propofol (10 M; added 10 min before the phenylephrine) or the Mas receptor antagonist A779 (10 M; added 30 min before phenylephrine) in separate experimental groups.

Role of Adiponectin Receptor 1 in Promoting Nitric Oxide-Mediated Flow-Induced Dilation in the Human Microvasculature.

Chronic administration of exogenous adiponectin restores nitric oxide (NO) as the mediator of flow-induced dilation (FID) in arterioles collected from patients with coronary artery disease (CAD). Here we hypothesize that this effect as well as NO signaling during flow during health relies on activation of Adiponectin Receptor 1 (AdipoR1). We further posit that osmotin, a plant-derived protein and AdipoR1 activator, is capable of eliciting similar effects as adiponectin.

Vascular endothelial adiponectin signaling across the life span.

Cardiovascular disease risk increases with age regardless of sex. Some of this risk is attributable to alterations in natural hormones throughout the life span. The quintessential example of this being the dramatic increase in cardiovascular disease following the transition to menopause.

Sweat the small stuff: The human microvasculature and heart disease.

Traditionally thought of primarily as the predominant regulator of myocardial perfusion, it is becoming more accepted that the human coronary microvasculature also exerts a more direct influence on the surrounding myocardium. Coronary microvascular dysfunction (CMD) not only precedes large artery atherosclerosis, but is associated with other cardiovascular diseases such as heart failure with preserved ejection fraction and hypertrophic cardiomyopathy. It is also highly predictive of cardiovascular events in patients with or without atherosclerotic cardiovascular disease.

Heart Failure With Preserved Ejection Fraction: A Comprehensive Review and Update of Diagnosis, Pathophysiology, Treatment, and Perioperative Implications.

Almost three-quarters of all heart failure patients who are older than 65 have heart failure with preserved ejection fraction (HFpEF). The proportion and hospitalization rate of patients with HFpEF are increasing steadily relative to patients in whom heart failure occurs as result of reduced ejection fraction. The predominance of the HFpEF phenotype most likely is explained by the prevalence of medical conditions associated with an aging population.

Crossing signals: bioactive lipids in the microvasculature.

The primary function of the arterial microvasculature is to ensure that regional perfusion of blood flow is matched to the needs of the tissue bed. This critical physiological mechanism is tightly controlled and regulated by a variety of vasoactive compounds that are generated and released from the vascular endothelium. Although these substances are required for modulating vascular tone, they also influence the surrounding tissue and have an overall effect on vascular, as well as parenchymal, homeostasis.

Characteristics associated with Publication of Randomized Controlled Trials in the Journal of Cardiothoracic and Vascular Anesthesia: A 15-Year Analysis, 2004-2018.

Randomized controlled trials (RCTs) provide important data to guide clinical decisions. Publication bias may limit the applicability of RCTs because many clinical investigators prefer to submit and journals more selectively accept studies with positive results. The authors tested the hypothesis that positive RCTs published in the Journal of Cardiothoracic and Vascular Anesthesia were more likely to be associated with factors known to predict publication of positive versus negative RCTs in other journals.

Manipulation of the Sphingolipid Rheostat Influences the Mediator of Flow-Induced Dilation in the Human Microvasculature.

Background Elevated levels of ceramide, a sphingolipid known to cause a transition from nitric oxide (NO)- to hydrogen peroxide-dependent flow-induced dilation (FID) in human arterioles, correlate with adverse cardiac events. However, elevations of ceramide are associated with changed concentrations of other sphingolipid metabolites. The effects of sphingolipid metabolites generated through manipulation of this lipid pathway on microvascular function are unknown.

Gender Composition and Trends of Journal of Cardiothoracic and Vascular Anesthesia Editorial Board Membership: A 33-Year Analysis, 1987-2019.

Objective: Gender disparities in editorial board composition exist in the vast majority of specialties including anesthesiology. If a similar lack of gender parity exists in cardiothoracic anesthesiology is unknown. The authors examined the gender composition and trends of the Journal of Cardiothoracic and Vascular Anesthesia (JCVA) editorial board from the initial year of its publication (1987) to 2019.

Detrimental effects of chemotherapy on human coronary microvascular function.

Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation.