leptin and Cerebrovascular-Disorders

Despite the well-known global impact of overweight and obesity in the incidence of cerebrovascular disease, many aspects of this association are still inconsistently defined. In this chapter we aim to present a critical review on the links between obesity and both ischemic and hemorrhagic stroke and discuss its influence on functional outcomes, survival, and current treatments to acute and chronic stroke. The role of cerebrovascular endothelial function and respective modulation is also described as well as its laboratory and clinical assessment. In this context, the major contributing mechanisms underlying obesity-induced cerebral endothelial function (adipokine secretion, insulin resistance, inflammation, and hypertension) are discussed. A special emphasis is given to the participation of adipokines in the pathophysiology of stroke, namely adiponectin, leptin, resistin, apelin, and visfatin.

Topics: Adipokines; Adiponectin; Apelin; Brain Ischemia; Cerebrovascular Disorders; Endothelium, Vascular; Humans; Hypertension; Inflammation; Insulin Resistance; Intracranial Hemorrhages; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Stroke

To analyze the significance of ezetimibe in combination with low- to moderate-intensity atorvastatin adjuvant aspirin therapy for cerebrovascular disease.. 110 patients with cerebrovascular disease treated in our hospital from June 2020 to June 2021 were selected and divided into 55 patients in the control group and 55 patients in the study group according to the lottery method. After a comprehensive examination, patients in the two groups should be given aspirin for treatment; the control group was treated with conventional dose of atorvastatin on top of the above, and the study group was given ezetimibe and medium-low-dose atorvastatin on top of aspirin treatment, activities of daily living (ADL) score, carotid artery intima-media thickness, lipid level, coagulation level, clinical effect, and adverse rate of the two groups which were tested and compared.. After treatment, ADL score, high-density leptin cholesterol (HDL-C), and ATIII levels increased, while carotid artery media thickness, triglyceride (TG), total cholesterol (TC), low-density leptin cholesterol (LDL-C), DD, PC, and hs-CRP levels decreased (. Ezetimibe combined with medium- and low-intensity atorvastatin with aspirin in the treatment of cerebrovascular diseases can effectively improve the coagulation function of patients, reduce the level of inflammatory factors in patients, and improve the level of blood lipids in patients, with high safety and worthy of clinical application.

Topics: Activities of Daily Living; Anticholesteremic Agents; Aspirin; Atorvastatin; C-Reactive Protein; Carotid Intima-Media Thickness; Cerebrovascular Disorders; Cholesterol, LDL; Ezetimibe; Humans; Leptin; Pyrroles; Treatment Outcome; Triglycerides

The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology.. Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594).. Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.

Topics: Adiponectin; Aged; Biomarkers; Carotid Stenosis; Cerebrovascular Disorders; Chemokines; Chi-Square Distribution; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Plaque, Atherosclerotic; Predictive Value of Tests; Prognosis; Resistin; Risk Assessment; Risk Factors; Rupture, Spontaneous; Severity of Illness Index

To investigate the characteristic changes in serum estradiol and leptin levels in patients with cerebral-cardiac syndrome (CCS) induced by subarachnoid hemorrhage (SAH).. Ninety-six female patients with early stage of SAH (within 48 h of onset), who were admitted in our department between February 2008 and February 2014, were included in this study. Clinical conditions of patients were rated using Hunt-Hess scale. Serum levels of estradiol, leptin and echocardiography were determined in patients with various neurological injuries as well as in post-SAH patients and patients with SAH-induced CCS.. No significant differences (p > 0.05) were observed in the levels of estradiol or leptin between patients with different Hunt-Hess grades. While serum levels of estradiol and leptin were significantly elevated in SAH and CCS patients compared to normal controls (p < 0.05) but the elevated levels were more profound in CCS patients. Meanwhile there were also variable extents of left ventricular expansion and decrease of ejection fraction in CCS patients, with the same trends of estradiol and leptin.. Thus the results show that a significant increase in estradiol and leptin levels occurred in post-SAH CCS patients.

Topics: Adult; Aged; Cerebrovascular Disorders; Estradiol; Female; Heart Diseases; Humans; Leptin; Middle Aged; Subarachnoid Hemorrhage; Syndrome; Ultrasonography

The adipocytokine leptin has distinct functions regulating vascular tone, inflammation, and collateral artery growth. Arteriogenesis is an inflammatory process and provides a mechanism to overcome the effects of vascular obstruction. We, therefore, tested the effects of leptin in hypoperfused rat brain (three-vessel occlusion). Systemic leptin administration for 1 week after occlusion surgery increased cerebral hemodynamic reserve similar to granulocyte-macrophage colony-stimulating factor (GM-CSF), as indicated by improved CO(2) reactivity (vehicle 0.53%±0.26% versus leptin 1.05%±0.6% per mm Hg arterial pCO(2), P<0.05). Infusion of microspheres under maximal vasodilation failed to show a positive effect of leptin on cerebral perfusion (vehicle 64.9%±4.5% versus leptin 66.3%±7.0%, occluded/nonoccluded hemisphere). Acute treatment with GM-CSF led to a significant increased CO(2) reactivity and cerebral perfusion (79.2%±8.1% versus 64.9%±4.5%, P<0.05). Vasoconstrictive response of isolated rat carotid artery rings, after phenylephrine was attenuated at 24  hours following preincubation with leptin, was unaffected by removal of endothelium but abrogated by coculture with N-(omega)-nitro-L-arginine methylester, pointing toward an inducible nitric oxide synthase-mediated mechanism. In chronic cerebral hypoperfusion, acute leptin treatment restored the hemodynamic reserve of the cerebral vasculature through its effects on vascular tone, while leaving vascular outward remodeling unaffected. Our results, for the first time, reveal a protective role of leptin on vascular function in hemodynamically compromised brain tissue.

Topics: Animals; Anterior Cerebral Artery; Body Weight; Carbon Dioxide; Carotid Arteries; Cell Proliferation; Cerebrovascular Circulation; Cerebrovascular Disorders; Granulocyte-Macrophage Colony-Stimulating Factor; Hemodynamics; Leptin; Male; Monocytes; Muscle Tonus; Muscle, Smooth, Vascular; Neovascularization, Physiologic; Nitric Oxide Synthase Type II; Oxygen Consumption; Phenylephrine; Posterior Cerebral Artery; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents

Serum concentrations of leptin was investigated in 40 patients with ischemic stroke, in context of the size of the lesion and also in 40 non-diseased controls, matched according to age, gender and waist hip ratio. Serum leptin concentrations were determined in ng/ml with ELISA and computer tomography (CT) scan was performed in patients to estimate lesion size in cms. Serum leptin concentrations were found to be significantly higher (p < 0.001) in stroke patients (51.61+1.39), compared with controls (37.76+1.207). Moreover, positive correlation (r=0.93) existed between serum leptin level and infarction size in patients with stroke.

Topics: Aged; Blood Glucose; Case-Control Studies; Cerebrovascular Disorders; Female; Humans; Leptin; Male; Middle Aged; Waist-Hip Ratio

It has been reported that alcohol stimulates appetite. We aimed to establish the association between leptin, as a major food intake regulating factor, and alcohol intake in patients with chronic manifest coronary artery or cerebrovascular disease.. A cross-sectional study of 820 subjects after acute coronary syndrome, coronary revascularization or after first ischemic stroke (the Czech part of EUROASPIRE III surveys). Leptin concentrations were evaluated among predefined categories of reported weekly alcohol intake: abstainers, light drinkers (up to 2 drinks weekly, 1-44 g of pure alcohol), mild regular drinkers (3-14 drinks weekly, 45-308 g) and moderate or heavy drinkers (more than 15 drinks, ≥ 309 g of alcohol).. Leptin showed a clear negative trend among the alcohol intake categories. Mild regular drinkers showed significantly lower leptin levels (9.3(8.2) ng/ml) compared with abstainers (18.7(18.7) ng/ml, P<0.0001) and light occasional drinkers (14.2(17.8) ng/ml, P=0.00064). The negative association between leptin and alcohol intake as a dependent variable remained significant even after adjustment for potential confounders in multiple linear regression analysis (P=0.00032).. Drinking of small amounts of alcohol was, in our setting, associated with decreased serum leptin concentration, with a possible benefit in terms of cardiovascular risk.

Topics: Aged; Alcohol Drinking; Cerebrovascular Disorders; Coronary Artery Disease; Cross-Sectional Studies; Ethanol; Female; Humans; Leptin; Male; Middle Aged; Risk Factors

To investigate adipocytokines in patients with ischemic cerebrovascular disease and to develop an association between them.. In this study plasma adiponectin, leptin and Interleukin 6 (IL 6) concentration were measured by ELISA. Blood glucose and lipid profile was done by standard kit methods.. A total of 80 subjects with and without CVD were studied. The mean plasma level of IL6 of the forty patients with ischemic CVD was significantly higher than that of the forty subjects without CVD (41.64 + 2.50 versus 22.76 + 0.76 pg/mL; P < 0.001). The mean plasma level of adiponectin was significantly lower in patients with ischemic CVD than that of subjects without CVD (4.36 +/- 0.21 microg/mL versus 6.9 +/-0.241microg/mL; P < 0.001). Serum leptin concentrations were significantly higher (p < 0.001) in stroke patients (51.61 + 1.39) as compared with controls (37.76 + 1.207). Leptin levels were significantly negatively correlated with adiponectin (P < 0.01) and significantly positively correlated (P < 0.01) with interleukin 6 in stroke patients.. Present report provides additional support to the evidence of involvement of cytokines in inflammatory immune response of patients with cerebrovascular disease.

Topics: Adiponectin; Aged; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Stroke

Carotid artery lesions from symptomatic patients are characterized by inflammation and neovascularization. The adipokine leptin promotes angiogenesis and activates inflammatory cells, and the leptin receptor (ob gene-encoded receptor), ObR, is expressed in advanced atherosclerotic lesions. The present study quantitatively analyzed ObR messenger RNA (mRNA) expression and immunoreactivity in carotid artery plaques from symptomatic and asymptomatic persons. Plaque angiogenesis, gene expression of vascular endothelial growth factor (VEGF), and macrophage density were also analyzed.. Carotid endarterectomy specimens were collected from 26 patients undergoing surgery for hemispheric cerebrovascular symptoms (n = 13) or progressive asymptomatic internal carotid stenosis (n = 13). A representative sample, including part of the most active site, was collected from each lesion and evaluated by real-time polymerase chain reaction analysis for ObR(long) and ObR(common) isoforms, VEGF(165), and macrophage adhesion molecule-1 (Mac-1) mRNA, and by immunohistochemistry for ObR, von Willebrand factor (vWF), and CD68 antigen expression.. All plaques exhibited advanced atherosclerosis (American Heart Association class IV through VI). Transcript levels were preferentially elevated in symptomatic plaques for ObR(long) (P = .0006) and ObR(common) (P = .033), with a simultaneous upregulation of VEGF(165) (P = .001) and Mac-1 mRNA expression (P = .003). Immunohistochemical analysis confirmed a significant increase of ObR antigen levels (P = .011) and CD68-positive inflammatory cells (P = .049) in symptomatic plaques, whereas neovascularization, evident in all plaques, was similar in both groups (P = .7).. The ObR(long) and ObR(common) genes are upregulated and their protein preferentially synthesized in clinically symptomatic carotid plaques. Moreover, ObR expression is positively correlated with augmentation of gene transcripts related to macrophage density and neovascularization. These data suggest that ObR(long) and ObR(common) may be linked with histologic features of carotid plaque instability, which are associated with cerebral ischemic symptoms.

Topics: Aged; Biomarkers; C-Reactive Protein; Carotid Stenosis; Cerebrovascular Disorders; Female; Humans; Immunohistochemistry; Interleukin-6; Leptin; Macrophage-1 Antigen; Macrophages; Male; Middle Aged; Neovascularization, Pathologic; Polymerase Chain Reaction; Protein Isoforms; Receptors, Leptin; RNA, Messenger; Up-Regulation; Vascular Endothelial Growth Factor A