Microvessel Density: Integrating Sex-Based Differences and Elevated Cardiovascular Risks in Metabolic Syndrome

Metabolic syndrome (MetS) is a complex pathological state consisting of metabolic risk factors such as hypertension, insulin resistance, and obesity. The interconnectivity of cellular pathways within various biological systems suggests that each individual component of MetS may share common pathological sources. Additionally, MetS is closely associated with vasculopathy, including a reduction in microvessel density (MVD) (rarefaction) and elevated risk for various cardiovascular diseases. Microvascular impairments may contribute to perfusion-demand mismatch, where local metabolic needs are insufficiently met due to the lack of nutrient and oxygen supply, thus creating pathological positive-feedback loops and furthering the progression of disease. Sexual dimorphism is evident in these underlying cellular mechanisms, which places males and females at different levels of risk for cardiovascular disease and acute ischemic events. Estrogen exhibits protective effects on the endothelium of pre-menopausal women, while androgens may be antagonistic to cardiovascular health. This review examines MetS and its influences on MVD, as well as sex differences relating to the components of MetS and cardiovascular risk profiles. Finally, translational relevance and interventions are discussed in the context of these sex-based differences.

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Cellular mechanisms underlying the cardiovascular actions of oestrogens

Clinical Science ◽

10.1042/cs20050084 ◽

2006 ◽

Vol 111 (2) ◽

pp. 107-118 ◽

Cited By ~ 37

Author(s):

Shanhong Ling ◽

Paul Komesaroff ◽

Krishnankutty Sudhir

Keyword(s):

Cardiovascular Health ◽

Cell Function ◽

Cellular Mechanisms ◽

Menopausal Women ◽

Wide Range ◽

Health And Disease ◽

Cardiovascular Cells ◽

Post Menopausal ◽

And Function ◽

Cellular Components

Although pre-menopausal women enjoy relative cardiovascular protection, hormone (oestrogen±progestin)-replacement therapy has not shown cardiovascular benefits in post-menopausal women, suggesting that the effects of oestrogens on the cardiovascular system are much more complex than previously expected. Endothelial cells, smooth muscle cells, cardiac myocytes and fibroblasts, the cellular components of blood vessels and the heart, play important roles in cardiovascular health and disease. During the development and progression of cardiovascular disease, changes occur both in the structure and function of these cells, resulting in a wide range of abnormalities, which affect growth, death and physiological function. These cells contain functional oestrogen receptors and are targets for oestrogen action. This review focuses on recent studies on the effects of oestrogen on cardiovascular cell function. Oestrogens, particularly 17β-oestradiol, exert multiple effects on cardiovascular cells, and these effects may contribute to the gender-associated protection against cardiovascular diseases.

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Adipokines: molecular links between obesity and atheroslcerosis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01058.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. H2031-H2041 ◽

Cited By ~ 511

Author(s):

David C. W. Lau ◽

Bikramjit Dhillon ◽

Hongyun Yan ◽

Paul E. Szmitko ◽

Subodh Verma

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Adipose Tissue ◽

Cardiovascular Health ◽

Clinical Evidence ◽

Therapeutic Strategies ◽

Cellular Mechanisms ◽

Treatment And Prevention ◽

Industrialized Nations

Atherosclerotic disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment, and prevention. The increasing epidemic of obesity, insulin resistance, and diabetes will likely add to this burden. Increasingly, it is becoming apparent that adipose tissue is an active endocrine and paracrine organ that releases several bioactive mediators that influence not only body weight homeostasis but also inflammation, coagulation, fibrinolysis, insulin resistance, diabetes, and atherosclerosis. The cellular mechanisms linking obesity and atherosclerosis are complex and have not been fully elucidated. This review summarizes the experimental and clinical evidence on how excess body fat influences cardiovascular health through multiple yet converging pathways. The role of adipose tissue in the development of obesity-linked insulin resistance, metabolic syndrome, and diabetes will be reviewed, including an examination of the molecular links between obesity and atherosclerosis, namely, the effects of fat-derived adipokines. Finally, we will discuss how these new insights may provide us with innovative therapeutic strategies to improve cardiovascular health.

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Association between the Mediterranean lifestyle, metabolic syndrome and mortality: a whole-country cohort in Spain

Cardiovascular Diabetology ◽

10.1186/s12933-020-01195-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mercedes Sotos-Prieto ◽

Rosario Ortolá ◽

Miguel Ruiz-Canela ◽

Esther Garcia-Esquinas ◽

David Martínez-Gómez ◽

...

Keyword(s):

Metabolic Syndrome ◽

Cardiovascular Mortality ◽

Cardiovascular Health ◽

Total Mortality ◽

Hdl Cholesterol ◽

Cardiometabolic Health ◽

The Metabolic Syndrome ◽

Mediterranean Countries ◽

Low Hdl ◽

The Mediterranean

Abstract Background Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain. Methods Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008–2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence). Results Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend < 0.001). During a mean follow-up of 8.7 years, 330 total deaths (74 CVD deaths) were ascertained. When comparing those in highest vs. lowest quartile of MEDLIFE, the multivariable-adjusted hazard ratio (95% CI) was 0.58 (0.37, 0.90) for total mortality and 0.33 (0.11, 1.02) for cardiovascular mortality. Conclusions The Mediterranean lifestyle was associated with lower frequency of MS and reduced all-cause mortality in Spain. Future studies should determine if this also applies to other Mediterranean countries, and also improve cardiovascular health outside the Mediterranean basin.

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Metabolic syndrome in premenopausal and postmenopausal women with type 2 diabetes: loss of protective effects of premenopausal status

Journal of Diabetes & Metabolic Disorders ◽

10.1186/s40200-014-0102-5 ◽

2014 ◽

Vol 13 (1) ◽

Cited By ~ 12

Author(s):

Manouchehr Nakhjavani ◽

Mehrnaz Imani ◽

Mehrdad Larry ◽

Arash Aghajani-Nargesi ◽

Afsaneh Morteza ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Postmenopausal Women ◽

Protective Effects

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Relation between uric acid and metabolic syndrome in subjects with cardiometabolic risk

Einstein (São Paulo) ◽

10.1590/s1679-45082015ao3194 ◽

2015 ◽

Vol 13 (2) ◽

pp. 202-208 ◽

Cited By ~ 14

Author(s):

Hellen Abreu da Silva ◽

Júlia Cristina Cardoso Carraro ◽

Josefina Bressan ◽

Helen Hermana Miranda Hermsdorff

Keyword(s):

Metabolic Syndrome ◽

Uric Acid ◽

Serum Uric Acid ◽

Abdominal Obesity ◽

Health Program ◽

Cardiovascular Health ◽

Cardiometabolic Risk ◽

Cross Sectional Study ◽

Cross Sectional ◽

Potential Biomarker

Objective To identify possible relations between serum uric acid levels and metabolic syndrome and its components in a population with cardiometabolic risk. Methods This cross-sectional study included 80 subjects (46 women), with mean age of 48±16 years, seen at the Cardiovascular Health Program. Results The prevalence of hyperuricemia and metabolic syndrome was 6.3% and 47.1%, respectively. Uric acid level was significantly higher in individuals with metabolic syndrome (5.1±1.6mg/dL), as compared to those with no syndrome or with pre-syndrome (3.9±1.2 and 4.1±1.3mg/dL, respectively; p<0.05). The uric acid levels were significantly higher in men presenting abdominal obesity, and among women with abdominal obesity, lower HDL-c levels and higher blood pressure (p<0.05). Conclusion Uric acid concentrations were positively related to the occurrence of metabolic syndrome and its components, and there were differences between genders. Our results indicate serum uric acid as a potential biomarker for patients with cardiometabolic risk.

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Ideal cardiovascular health in adolescence is associated with reduced risks of hypertension, metabolic syndrome and high cholesterol in adulthood

Evidence-Based Nursing ◽

10.1136/eb-2012-100887 ◽

2012 ◽

Vol 16 (1) ◽

pp. 24-25 ◽

Cited By ~ 1

Author(s):

Laura L Hayman ◽

Sarah M Camhi

Keyword(s):

Metabolic Syndrome ◽

Cardiovascular Health ◽

High Cholesterol ◽

Ideal Cardiovascular Health

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A Comparative Study of Lipid Profile and Atherogenic Index of Plasma Among the Pre and Post-Menopausal Women

Anwer Khan Modern Medical College Journal ◽

10.3329/akmmcj.v9i1.35824 ◽

2018 ◽

Vol 9 (1) ◽

pp. 44-49 ◽

Cited By ~ 1

Author(s):

Sadia Khanduker ◽

Rumana Ahmed ◽

Mafruha Nazneen ◽

Anawarul Alam ◽

Farhana Khondokar

Keyword(s):

Risk Factor ◽

Lipid Profile ◽

Independent Risk Factor ◽

Cardiovascular Health ◽

Premenopausal Women ◽

Atherogenic Index ◽

Mathematical Methods ◽

Atherogenic Index Of Plasma ◽

Menopausal Women ◽

Post Menopausal

Background: Menopausal health in our environment has received little attention. As a independent risk factor for dyslipidemia, the degree and pattern of derangement, though difficult to assess may adversely affect the cardiovascular health of our women.Objectives: To estimate the serum lipid profile and the atherogenic index of plasma among the pre and post- menopausal women.Materials and Methods: After an overnight fasting blood samples were collected from a group of 339 women, 140 premenopausal aged between 25-50 years and 199 postmenopausal aged between 51-70 years. Serum total cholesterol (TC), triglycerides (TG) and HDL-cholesterol were estimated by enzymatic methods and LDL-cholesterol by established mathematical methods. Atherogenic index of plasma (AIP) were calculated by using the formula (logTG/HDL-C). Statistical analysis was carried out in the two groups using the unpaired t test. Results were expressed as mean±SD. P values <0.05 were considered to be statistically significant.Results: There were statistically significant increase in serum TC (191.21±45.50 mg/dl), TG (185.83± 111.83 mg/dl) and LDL-C (118.71±38.48 mg/dl) in post-menopausal women. Their HDL-C level (38.67±10.00mg/dl) was significantly decreased. The calculated atherogenic index of plasma (AIP) was significantly higher (0.63±0.27) in post-menopausal women as compared to that in premenopausal women (0.50±0.29).Conclusion: Menopause leads to changes in lipid profile. By elevating LDL and the reduction of cardioprotective HDL is an indication that menopause is an independent risk factor for developing cardiovascular disease. These changes are caused by loss of cardio-protective effect of oestrogen.Anwer Khan Modern Medical College Journal Vol. 9, No. 1: Jan 2018, P 44-49

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Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

Science Advances ◽

10.1126/sciadv.aax6208 ◽

2020 ◽

Vol 6 (1) ◽

pp. eaax6208 ◽

Cited By ~ 16

Author(s):

Su-Ling Zeng ◽

Shang-Zhen Li ◽

Ping-Ting Xiao ◽

Yuan-Yuan Cai ◽

Chu Chu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Amino Acid ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Amplicon Sequencing ◽

Therapeutic Interventions ◽

Protective Effects ◽

Fecal Microbiome ◽

Metabolomic Profiling ◽

Branched Chain

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

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Antioxidant and Anti-inflammatory Mechanisms of Astaxanthin in Cardiovascular Diseases

10.20944/preprints202008.0119.v1 ◽

2020 ◽

Author(s):

Carolina Parga Martins Pereira ◽

Ana Carolina Remondi Souza ◽

Andrea Rodrigues Vasconcelos ◽

Pietra Sacramento Prado ◽

José João Name

Keyword(s):

Cardiovascular Diseases ◽

Molecular Mechanisms ◽

Cardiovascular Health ◽

Redox Balance ◽

Cellular Mechanisms ◽

Positive Effects ◽

Antioxidant Agents ◽

Therapeutic Properties ◽

Anti Inflammatory ◽

Preclinical And Clinical Studies

Cardiovascular disease is the most common cause of death. Oxidative stress and inflammation are pathophysiological processes involved in the development of cardiovascular diseases, so anti-inflammatory and antioxidant agents that modulate redox balance have become the targets of research to evaluate their molecular mechanisms and therapeutic properties. Astaxanthin, a carotenoid of the xanthophyll group, has potent antioxidant effects due to its molecular structure and its arrangement in the plasma membrane, factors that favor the neutralization of reactive oxygen and nitrogen species. This carotenoid also stands out for its anti-inflammatory activity, possibly interrelated with its antioxidant effect, as well as for its modulation of lipid and glucose metabolism. Considering the potential positive effects of astaxanthin on cardiovascular health evidenced by preclinical and clinical studies, this paper describes the molecular and cellular mechanisms related to the antioxidant and anti-inflammatory properties of this carotenoid in cardiovascular diseases, especially atherosclerosis.

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