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Circulation Research Apr 2021Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin... (Review)
Review
Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.
Topics: Adipose Tissue; Adiposity; Animals; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Heart Disease Risk Factors; Homeostasis; Humans; Hypertension; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Mice; Obesity; Overweight; Subcutaneous Fat; Vascular Diseases; Vascular Stiffness; Vasoconstriction
PubMed: 33793327
DOI: 10.1161/CIRCRESAHA.121.318093 -
Circulation Research May 2021Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and... (Review)
Review
Acute decompensated heart failure (ADHF) is one of the leading admission diagnoses worldwide, yet it is an entity with incompletely understood pathophysiology and limited therapeutic options. Patients admitted for ADHF have high in-hospital morbidity and mortality, as well as frequent rehospitalizations and subsequent cardiovascular death. This devastating clinical course is partly due to suboptimal medical management of ADHF with persistent congestion upon hospital discharge and inadequate predischarge initiation of life-saving guideline-directed therapies. While new drugs for the treatment of chronic HF continue to be approved, there has been no new therapy approved for ADHF in decades. This review will focus on the current limited understanding of ADHF pathophysiology, possible therapeutic targets, and current limitations in expanding available therapies in light of the unmet need among these high-risk patients.
Topics: Acute Disease; Body Fluids; Cardio-Renal Syndrome; Cardiotoxins; Comorbidity; Heart Failure; Hospitalization; Humans; Inflammation Mediators; Myocardial Contraction; Natriuretic Peptide, Brain; Patient Discharge; Patient Readmission; Renin-Angiotensin System; Symptom Assessment; Vascular Resistance; Vasoconstriction; Vasodilator Agents
PubMed: 33983837
DOI: 10.1161/CIRCRESAHA.121.318186 -
Arteriosclerosis, Thrombosis, and... Sep 2019While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and... (Review)
Review
While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and accidents, the leading cause of death in methamphetamine users is cardiovascular disease, because of significant effects of methamphetamine on vasoconstriction, pulmonary hypertension, atherosclerotic plaque formation, cardiac arrhythmias, and cardiomyopathy. In this review, we examine the current literature on methamphetamine-induced changes in cardiovascular health, discuss the potential mechanisms regulating these varied effects, and highlight our deficiencies in understanding how to treat methamphetamine-associated cardiovascular dysfunction.
Topics: Arrhythmias, Cardiac; Atherosclerosis; Cardiomyopathies; Cardiovascular Diseases; Humans; Hypertension, Pulmonary; Methamphetamine; Vasoconstriction
PubMed: 31433698
DOI: 10.1161/ATVBAHA.119.312461 -
Journal of Biomedical Science Sep 2022Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder being recognized during the past two decades. It is characterized by multiple... (Review)
Review
Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder being recognized during the past two decades. It is characterized by multiple abrupt severe headaches and widespread cerebral vasoconstrictions, with potential complications such as ischemic stroke, convexity subarachnoid hemorrhage, intracerebral hemorrhage and posterior reversible encephalopathy syndrome. The clinical features, imaging findings, and dynamic disease course have been delineated. However, the pathophysiology of RCVS remains elusive. Recent studies have had substantial progress in elucidating its pathogenesis. It is now believed that dysfunction of cerebral vascular tone and impairment of blood-brain barrier may play key roles in the pathophysiology of RCVS, which explains some of the clinical and radiological manifestations of RCVS. Some other potentially important elements include genetic predisposition, sympathetic overactivity, endothelial dysfunction, and oxidative stress, although the detailed molecular mechanisms are yet to be identified. In this review, we will summarize what have been revealed in the literature and elaborate how these factors could contribute to the pathophysiology of RCVS.
Topics: Brain; Cerebral Hemorrhage; Humans; Posterior Leukoencephalopathy Syndrome; Vasoconstriction; Vasospasm, Intracranial
PubMed: 36127720
DOI: 10.1186/s12929-022-00857-4 -
La Radiologia Medica Sep 2022Reversible cerebral vasoconstriction syndrome (RCVS) is a group of disorders characterized by segmental narrowing and dilatation of medium-to-large cerebral arteries,... (Review)
Review
Reversible cerebral vasoconstriction syndrome (RCVS) is a group of disorders characterized by segmental narrowing and dilatation of medium-to-large cerebral arteries, clinically presenting with recurrent episodes of sudden-onset thunderclap headaches, with or without focal neurological deficits. Cerebral vasoconstriction is typically reversible, with spontaneous resolution within 3 months. Although the syndrome has generally a benign course, patients with neurological deficits may experience worse outcome. The main imaging finding is segmental constriction of intracranial arteries, which can be associated with subarachnoid hemorrhage and/or ischemic foci. Other possible findings are intracranial hemorrhage, subdural bleeding and cerebral edema. The latter may have a pattern which can resemble that of posterior reversible encephalopathy syndrome, a condition that can overlap with RCVS. New imaging techniques, such as vessel wall imaging and arterial spin labeling, are proving useful in RCVS and are giving new insights into the pathophysiology of this condition. In this paper, we aim to review neuroimaging findings of RCVS.
Topics: Cerebrovascular Disorders; Headache Disorders, Primary; Humans; Neuroimaging; Posterior Leukoencephalopathy Syndrome; Vasoconstriction; Vasospasm, Intracranial
PubMed: 35932443
DOI: 10.1007/s11547-022-01532-2 -
The Journal of Headache and Pain Jun 2020Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to... (Review)
Review
Migraine is a leading cause of disability worldwide, but it is still underdiagnosed and undertreated. Research on the pathophysiology of this neurological disease led to the discovery that calcitonin gene-related peptide (CGRP) is a key neuropeptide involved in pain signaling during a migraine attack. CGRP-mediated neuronal sensitization and glutamate-based second- and third-order neuronal signaling may be an important component involved in migraine pain. The activation of several serotonergic receptor subtypes can block the release of CGRP, other neuropeptides, and neurotransmitters, and can relieve the symptoms of migraine. Triptans were the first therapeutics developed for the treatment of migraine, working through serotonin 5-HT receptors. The discovery that the serotonin 1F (5-HT) receptor was expressed in the human trigeminal ganglion suggested that this receptor subtype may have a role in the treatment of migraine. The 5-HT receptor is found on terminals and cell bodies of trigeminal ganglion neurons and can modulate the release of CGRP from these nerves. Unlike 5-HT receptors, the activation of 5-HT receptors does not cause vasoconstriction.The potency of different serotonergic agonists towards 5-HT was correlated in an animal model of migraine (dural plasma protein extravasation model) leading to the development of lasmiditan. Lasmiditan is a newly approved acute treatment for migraine in the United States and is a lipophilic, highly selective 5-HT agonist that can cross the blood-brain barrier and act at peripheral nervous system (PNS) and central nervous system (CNS) sites.Lasmiditan activation of CNS-located 5-HT receptors (e.g., in the trigeminal nucleus caudalis) could potentially block the release of CGRP and the neurotransmitter glutamate, thus preventing and possibly reversing the development of central sensitization. Activation of 5-HT receptors in the thalamus can block secondary central sensitization of this region, which is associated with progression of migraine and extracephalic cutaneous allodynia. The 5-HT receptors are also elements of descending pain modulation, presenting another site where lasmiditan may alleviate migraine. There is emerging evidence that mitochondrial dysfunction might be implicated in the pathophysiology of migraine, and that 5-HT receptors can promote mitochondrial biogenesis. While the exact mechanism is unknown, evidence suggests that lasmiditan can alleviate migraine through 5-HT agonist activity that leads to inhibition of neuropeptide and neurotransmitter release and inhibition of PNS trigeminovascular and CNS pain signaling pathways.
Topics: Animals; Benzamides; Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Neurons; Piperidines; Pyridines; Receptors, Serotonin; Serotonin Receptor Agonists; Trigeminal Ganglion; Tryptamines; Vasoconstriction; Receptor, Serotonin, 5-HT1F
PubMed: 32522164
DOI: 10.1186/s10194-020-01132-3 -
Science (New York, N.Y.) Mar 2020Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and...
Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.
Topics: Animals; Aquaporin 5; Brain Edema; Glymphatic System; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Stroke; Vasoconstriction
PubMed: 32001524
DOI: 10.1126/science.aax7171 -
European Review For Medical and... May 2021We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS).
OBJECTIVE
We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS).
MATERIALS AND METHODS
Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected.
RESULTS
The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS.
CONCLUSIONS
In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.
Topics: Cerebrovascular Disorders; Headache Disorders, Primary; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Vasoconstriction
PubMed: 34002826
DOI: 10.26355/eurrev_202105_25834 -
Proceedings of the National Academy of... Dec 2021Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood...
Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood vessels. Macroglia, such as astrocytes and Müller cells, contribute to this neurovascular unit within the brain and retina, respectively. This study explored the role of microglia, the innate immune cell of the CNS, in retinal vasoregulation, and highlights changes during early diabetes. Structurally, microglia were found to contact retinal capillaries and neuronal synapses. In the brain and retinal explants, the addition of fractalkine, the sole ligand for monocyte receptor Cx3cr1, resulted in capillary constriction at regions of microglial contact. This vascular regulation was dependent on microglial Cx3cr1 involvement, since genetic and pharmacological inhibition of Cx3cr1 abolished fractalkine-induced constriction. Analysis of the microglial transcriptome identified several vasoactive genes, including angiotensinogen, a constituent of the renin-angiotensin system (RAS). Subsequent functional analysis showed that RAS blockade via candesartan abolished microglial-induced capillary constriction. Microglial regulation was explored in a rat streptozotocin (STZ) model of diabetic retinopathy. Retinal blood flow was reduced after 4 wk due to reduced capillary diameter and this was coincident with increased microglial association. Functional assessment showed loss of microglial-capillary response in STZ-treated animals and transcriptome analysis showed evidence of RAS pathway dysregulation in microglia. While candesartan treatment reversed capillary constriction in STZ-treated animals, blood flow remained decreased likely due to dilation of larger vessels. This work shows microglia actively participate in the neurovascular unit, with aberrant microglial-vascular function possibly contributing to the early vascular compromise during diabetic retinopathy.
Topics: Animals; Benzimidazoles; Biphenyl Compounds; Chemokine CX3CL1; Diabetic Retinopathy; Gene Expression Profiling; Mice; Microglia; Neurons; Pericytes; Rats; Renin-Angiotensin System; Retina; Retinal Vessels; Signal Transduction; Streptozocin; Tetrazoles; Vasoconstriction
PubMed: 34903661
DOI: 10.1073/pnas.2112561118 -
Arteriosclerosis, Thrombosis, and... Nov 2019Perivascular adipocytes residing in the vascular adventitia are recognized as distinct endocrine cells capable of responding to inflammatory stimuli and communicating... (Review)
Review
Perivascular adipocytes residing in the vascular adventitia are recognized as distinct endocrine cells capable of responding to inflammatory stimuli and communicating with the sympathetic nervous system and adjacent blood vessel cells, thereby releasing adipocytokines and other signaling mediators to maintain vascular homeostasis. Perivascular adipocytes exhibit phenotypic heterogeneity (both white and brown adipocytes) and become dysfunctional in conditions, such as diet-induced obesity, thus promoting vascular inflammation, vasoconstriction, and smooth muscle cell proliferation to potentially contribute to the development of vascular diseases, such as atherosclerosis, hypertension, and aortic aneurysms. Although accumulating data have advanced our understanding of the role of perivascular adipocytes in modulating vascular function, their impact on vascular disease, particularly in humans, remains to be fully defined. This brief review will discuss the mechanisms whereby perivascular adipocytes regulate vascular disease, with a particular emphasis on recent findings and current limitations in the field of research.
Topics: Adipocytes; Adipokines; Animals; Computed Tomography Angiography; Endothelium, Vascular; Humans; Obesity; Phenotype; Signal Transduction; Vascular Diseases; Vasoconstriction; Vasodilation
PubMed: 31510794
DOI: 10.1161/ATVBAHA.119.312304