scholarly journals Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor

2008 ◽  
Vol 197 (3) ◽  
pp. 447-462 ◽  
Author(s):  
Inmaculada C Villar ◽  
Adrian J Hobbs ◽  
Amrita Ahluwalia
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Vascular Function ◽  
Vascular Tone ◽  
Inflammatory Responses ◽  
Vascular Inflammation ◽  
Critical Role ◽  
Premenopausal Women ◽  
Circulating Cells ◽  
Inflammatory Processes

The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.

scholarly journals Sex Differences in Stroke

2012 ◽  
Vol 32 (12) ◽  
pp. 2100-2107 ◽  
Author(s):  
Roy AM Haast ◽  
Deborah R Gustafson ◽  
Amanda J Kiliaan
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Premenopausal Women ◽  
Epidemiologic Studies ◽  
Stroke Onset ◽  
Effective Prevention ◽  
Sex Steroid Hormone ◽  
Incidence And Mortality ◽  
Primary Focus ◽  
The Impact

Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment.

scholarly journals Vascular Aging in Rodent Models: Contrasting Mechanisms Driving the Female and Male Vascular Senescence

2021 ◽  
Vol 2 ◽  
Author(s):  
Paula R. Barros ◽  
Tiago J. Costa ◽  
Eliana H. Akamine ◽  
Rita C. Tostes
Keyword(s):  
Sex Differences ◽  
Animal Models ◽  
Vascular Function ◽  
Metabolic Diseases ◽  
Vascular Dysfunction ◽  
Laboratory Animals ◽  
Aging Research ◽  
Aging Studies ◽  
Inflammatory Processes ◽  
Vascular Senescence

Increasing scientific interest has been directed to sex as a biological and decisive factor on several diseases. Several different mechanisms orchestrate vascular function, as well as vascular dysfunction in cardiovascular and metabolic diseases in males and females. Certain vascular sex differences are present throughout life, while others are more evident before the menopause, suggesting two important and correlated drivers: genetic and hormonal factors. With the increasing life expectancy and aging population, studies on aging-related diseases and aging-related physiological changes have steeply grown and, with them, the use of aging animal models. Mouse and rat models of aging, the most studied laboratory animals in aging research, exhibit sex differences in many systems and physiological functions, as well as sex differences in the aging process and aging-associated cardiovascular changes. In the present review, we introduce the most common aging and senescence-accelerated animal models and emphasize that sex is a biological variable that should be considered in aging studies. Sex differences in the cardiovascular system, with a focus on sex differences in aging-associated vascular alterations (endothelial dysfunction, remodeling and oxidative and inflammatory processes) in these animal models are reviewed and discussed.

scholarly journals Sex Differences in Otolaryngology: Focus on the Emerging Role of Estrogens in Inflammatory and Pro-Resolving Responses

2021 ◽  
Vol 22 (16) ◽  
pp. 8768
Author(s):  
Sheng-Dean Luo ◽  
Tai-Jan Chiu ◽  
Wei-Chih Chen ◽  
Ching-Shuen Wang
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Immune Cells ◽  
Vocal Fold ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Proinflammatory Responses ◽  
Males And Females ◽  
Nose And Throat

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in ENT diseases are linked to the level of sex hormones. The sex hormone receptors are present on a wide variety of immune cells; therefore, it is evident that they play crucial roles in regulating the immune system and hence affect the disease progression of ENT diseases. In this review, we focus on how sex hormones, particularly estrogens, regulate ENT diseases, such as chronic rhinosinusitis, vocal fold polyps, thyroid cancer, Sjögren’s syndrome, and head and neck cancers, from the perspectives of inflammatory responses and specialized proresolving mediator-driven resolution. This paper aims to clarify why considering sex differences in the field of basic and medical research on otolaryngology is a key component to successful therapy for both males and females in the future.

scholarly journals Sex Differences in Molecular Mechanisms of Cardiovascular Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Vanessa Dela Justina ◽  
Jéssica S. G. Miguez ◽  
Fernanda Priviero ◽  
Jennifer C. Sullivan ◽  
Fernanda R. Giachini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Postmenopausal Women ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
Premenopausal Women ◽  
Western World ◽  
Autonomic Tone ◽  
Biological Sex ◽  
Cardiovascular Aging

Cardiovascular disease (CVD) is still the leading cause of illness and death in the Western world. Cardiovascular aging is a progressive modification occurring in cardiac and vascular morphology and physiology where increased endothelial dysfunction and arterial stiffness are observed, generally accompanied by increased systolic blood pressure and augmented pulse pressure. The effects of biological sex on cardiovascular pathophysiology have long been known. The incidence of hypertension is higher in men, and it increases in postmenopausal women. Premenopausal women are protected from CVD compared with age-matched men and this protective effect is lost with menopause, suggesting that sex-hormones influence blood pressure regulation. In parallel, the heart progressively remodels over the course of life and the pattern of cardiac remodeling also differs between the sexes. Lower autonomic tone, reduced baroreceptor response, and greater vascular function are observed in premenopausal women than men of similar age. However, postmenopausal women have stiffer arteries than their male counterparts. The biological mechanisms responsible for sex-related differences observed in cardiovascular aging are being unraveled over the last several decades. This review focuses on molecular mechanisms underlying the sex-differences of CVD in aging.

Interleukin-10 in the Vasculature: Pathophysiological Implications

2021 ◽  
Vol 20 ◽  
Author(s):  
Raiany Alves de Freitas ◽  
Victor Vitorino Lima ◽  
Gisele Facholi Bomfim ◽  
Fernanda Regina Casagrande Giachini
Keyword(s):  
Intracellular Signaling ◽  
Vascular Function ◽  
Vascular Tone ◽  
Vascular Tissue ◽  
Interleukin 10 ◽  
Vital Role ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Intracellular Pathway ◽  
Potential Use

Abstract: Interleukin-10 (IL-10) is an important immunomodulatory cytokine, initially characterized as an anti-inflammatory agent released by immune cells during infectious and inflammatory processes. IL-10 exhibits biological functions that extend to the regulation of different intracellular signaling pathways directly associated with vascular function. This cytokine plays a vital role in vascular tone regulation through the change of important proteins involved in vasoconstriction and vasodilation. Numerous investigations covered here have shown that therapeutic strategies inducing IL-10 result in anti-inflammatory, anti-hypertrophic, antihyperplastic, anti-apoptotic and antihypertensive effects. This non-systematic review summarizes the modulating effects mediated by IL-10 in vascular tissue, particularly on vascular tone, and the intracellular pathway induced by this cytokine. We also highlight the advances in IL-10 manipulation as a therapeutic target in different cardiovascular pathophysiologies, including the physiological implications in animals and humans. Finally, the review illustrates current and potential future perspectives of the potential use of IL-10 in clinical trials, based on the clinical evidence.

scholarly journals RAS and sex differences in diabetic nephropathy

2016 ◽  
Vol 310 (10) ◽  
pp. F945-F957 ◽  
Author(s):  
Sergi Clotet ◽  
Marta Riera ◽  
Julio Pascual ◽  
María José Soler
Keyword(s):  
Sex Differences ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Sex Hormones ◽  
Diabetic Kidney Disease ◽  
Kidney Diseases ◽  
Critical Role ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Diabetic Kidney

The incidence and progression of kidney diseases are influenced by sex. The renin-angiotensin system (RAS) is an important regulator of cardiovascular and renal function. Sex differences in the renal response to RAS blockade have been demonstrated. Circulating and renal RAS has been shown to be altered in type 1 and type 2 diabetes; this enzymatic cascade plays a critical role in the development of diabetic nephropathy (DN). Angiotensin-converting enzyme (ACE) and ACE2 are differentially regulated depending on its localization within the diabetic kidney. Furthermore, clinical and experimental studies have shown that circulating levels of sex hormones are clearly modulated in the context of diabetes, suggesting that sex-dependent RAS regulation may also be affected in these individuals. The effect of sex hormones on circulating and renal RAS may be involved in the sex differences observed in DN progression. In this paper we will review the influence of sex hormones on RAS expression and its relation to diabetic kidney disease. A better understanding of the sex dimorphism on RAS might provide a new approach for diabetic kidney disease treatment.

scholarly journals Sex differences in the vascular function and related mechanisms: role of 17β-estradiol

2018 ◽  
Vol 315 (6) ◽  
pp. H1499-H1518 ◽  
Author(s):  
Mallikarjuna R. Pabbidi ◽  
Maniselvan Kuppusamy ◽  
Sean P. Didion ◽  
Padmaja Sanapureddy ◽  
Joey T. Reed ◽  
...  
Keyword(s):  
Sex Differences ◽  
Postmenopausal Women ◽  
Vascular Function ◽  
Cochrane Review ◽  
Premenopausal Women ◽  
Sex Hormone ◽  
Vascular Structure ◽  
Beneficial Effects ◽  
17Β Estradiol

The incidence of cardiovascular disease (CVD) is lower in premenopausal women but increases with age and menopause compared with similarly aged men. Based on the prevalence of CVD in postmenopausal women, sex hormone-dependent mechanisms have been postulated to be the primary factors responsible for the protection from CVD in premenopausal women. Recent Women’s Health Initiative studies, Cochrane Review studies, the Early Versus Late Intervention Trial with Estradiol Study, and the Kronos Early Estrogen Prevention Study have suggested that beneficial effects of hormone replacement therapy (HRT) are seen in women of <60 yr of age and if initiated within <10 yr of menopause. In contrast, the beneficial effects of HRT are not seen in women of >60 yr of age and if commenced after 10 yr of menopause. The higher incidence of CVD and the failure of HRT in postmenopausal aged women could be partly associated with fundamental differences in the vascular structure and function between men and women and in between pre- and postmenopausal women, respectively. In this regard, previous studies from human and animal studies have identified several sex differences in vascular function and associated mechanisms. The female sex hormone 17β-estradiol regulates the majority of these mechanisms. In this review, we summarize the sex differences in vascular structure, myogenic properties, endothelium-dependent and -independent mechanisms, and the role of 17β-estradiol in the regulation of vascular function.

scholarly journals Transcriptomic Data Analysis Reveals a Down-Expression of Galectin-8 in Schizophrenia Hippocampus

2021 ◽  
Vol 11 (8) ◽  
pp. 973
Author(s):  
Maria Cristina Petralia ◽  
Rosella Ciurleo ◽  
Alessia Bramanti ◽  
Placido Bramanti ◽  
Andrea Saraceno ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Antipsychotic Agents ◽  
Standards Of Care ◽  
Specific Gene ◽  
Contributing Factors ◽  
Healthy Donors ◽  
Dorsolateral Prefrontal ◽  
Inflammatory Processes ◽  
Disease Specific

Schizophrenia (SCZ) is a severe psychiatric disorder with several clinical manifestations that include cognitive dysfunction, decline in motivation, and psychosis. Current standards of care treatment with antipsychotic agents are often ineffective in controlling the disease, as only one-third of SCZ patients respond to medications. The mechanisms underlying the pathogenesis of SCZ remain elusive. It is believed that inflammatory processes may play a role as contributing factors to the etiology of SCZ. Galectins are a family of β-galactoside-binding lectins that contribute to the regulation of immune and inflammatory responses, and previous reports have shown their role in the maintenance of central nervous system (CNS) homeostasis and neuroinflammation. In the current study, we evaluated the expression levels of the galectin gene family in post-mortem samples of the hippocampus, associative striatum, and dorsolateral prefrontal cortex from SCZ patients. We found a significant downregulation of LGALS8 (Galectin-8) in the hippocampus of SCZ patients as compared to otherwise healthy donors. Interestingly, the reduction of LGALS8 was disease-specific, as no modulation was observed in the hippocampus from bipolar nor major depressive disorder (MDD) patients. Prediction analysis identified TBL1XR1, BRF2, and TAF7 as potential transcription factors controlling LGALS8 expression. In addition, MIR3681HG and MIR4296 were negatively correlated with LGALS8 expression, suggesting a role for epigenetics in the regulation of LGALS8 levels. On the other hand, no differences in the methylation levels of LGALS8 were observed between SCZ and matched control hippocampus. Finally, ontology analysis of the genes negatively correlated with LGALS8 expression identified an enrichment of the NGF-stimulated transcription pathway and of the oligodendrocyte differentiation pathway. Our study identified LGALS8 as a disease-specific gene, characterizing SCZ patients, that may in the future be exploited as a potential therapeutic target.

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