Mineralocorticoids and Cardiovascular Disease in Females with Insulin Resistance and Obesity

Nayyar, Manav; Lastra, Guido; Acevedo, Camila Manrique

doi:10.1007/s11906-018-0887-6

Cited by 5 publications

(4 citation statements)

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“…Our study further extends our knowledge on the role of myeloid MR activation in mediating vascular stiffening in female mice, which have been shown to be more vulnerable to vascular dysfunction in the setting of elevated aldosterone levels when compared with males (Manrique et al, 2016;Davel et al, 2018). In this study, we did not compare females to males; however, our data support the notion that MR activation contributes to profound vascular dysfunction in females in conditions of enhanced RAAS activity such as obesity and insulin resistance (Mehta et al, 2016;Davel et al, 2018;Nayyar et al, 2018;Shukri et al, 2018).…”

Section: Discussionsupporting

confidence: 70%

“…In the vasculature, mineralocorticoids elicit dimorphic responses that impact females to a greater extent compared to males ( Mehta et al, 2016 ). Indeed, obese and insulin-resistant women display more frequent and aggressive frequency of CVD compared to men ( Nayyar et al, 2018 ). Although available clinical and preclinical studies have established that MR activation is critical to the development of vascular dysfunction impacting females more severely than males, there is still a lack of knowledge about the relationship between MR activation in myeloid cells and the development of vascular/endothelial dysfunction in females.…”

Section: Introductionmentioning

confidence: 99%

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Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice

et al. 2021

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Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in females via increased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessed via atomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice

et al. 2021

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“…The occurrence of IR will not only increase the incidence of diseases such as type 2 diabetes, hypertension, coronary artery disease, stroke, etc. but also increase all-cause mortality of patients with cancer, causing trillions of medical burdens worldwide ( 8 , 30 , 31 , 32 , 33 , 34 , 35 ). The incidence of IR, which remains on the rise, is largely attributable to the failure to recognize its occurrence early.…”

Section: Discussionmentioning

confidence: 99%

Using optimal subset regression to identify factors associated with insulin resistance and construct predictive models in the US adult population

Gong

Liu

Luo

et al. 2022

Endocrine Connections

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Background: In recent decades, with the development of the global economy and the improvement of living standards, insulin resistance (IR) has become a common phenomenon. Current studies have shown that IR varies between races. Therefore, it is necessary to develop individual prediction models for each country. The purpose of this study was to develop a predictive model of IR applicable to the US population. Method: 11 cycles of data from the NHANES database were selected for this study. Of these, participants from 1999 to 2010 (n= 14931) were used to establish the model, and participants from 2011 to 2020 (n= 13646) were used to validate the model. Univariate and multivariate logistic regression were used to analyze the factors associated with IR. Optimal subset regression was used to filter the best modeling variables. ROC curves, calibration curves, and decision curve analysis curves were used to determine the strengths and weaknesses of the model. Results: After screening the variables by optimal subset regression, variables with covariance were excluded, and a total of 7 factors (including HDL, LDL, ALB, GLB, GLU, BMI, and waist) were finally included to establish the prediction model. The AUCs were 0.851 and 0.857 in the training and validation sets, respectively, and the Brier value of the calibration curve was 0.153. Conclusion: The optimal subset predictive model proposed in this study has a great performance in predicting IR, and the decision curve analysis shows that it has a high net clinical benefit, which can help clinicians and epidemiologists easily detect IR and take appropriate interventions as early as possible. Keywords: Insulin resistance; Optimal subset regression; Calibration curves; NHANES; HOMA-IR

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“…Obesity, as a chronic disease, has become one of the most serious public health threats of the 21st century [2]. Many studies have noted that obesity and being overweight are generally accompanied by one or more risk factors of cardiovascular disease [3][4][5]. Obesity not only has an association with cardiovascular diseases but also a major cause of liver dysfunction and other related diseases.…”

Section: Introductionmentioning

confidence: 99%

Effect of a combination of aerobic exercise and dietary modiﬁcation on liver function in overweight and obese men

2021

JOMH

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Background: Obesity is not only associated with cardiovascular diseases but also a primary cause of liver dysfunction and other related diseases. This study's aim was to determine the impact of a combination of dietary modiﬁcation and aerobic exercise on liver function in overweight and obese adult males. Methods: 45 overweight or obese men were randomly divided between the control group (n = 22) and intervention group (n = 23). Subjects in the intervention group were provided with dietary modiﬁcation and aerobic exercise programmes. Dietary modiﬁcation is a diet which restricts calorie intake and balances nutrients. Before and after 12 weeks of intervention, participants' anthropometric characteristics and biochemical parameters relating to liver function including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were measured. Results: 12 weeks of aerobic exercise and dietary modiﬁcation resulted in average weight loss of 10.6%, and body mass index, waist circumference and fat percentage decreased by 10.2%, 9.4% and 14.5% (P < 0.05). AST, ALT, GGT and ALP in the intervention group reduced by 20.6%, 18.1%, 37.7% and 6.1% (P < 0.05). Compared to the control group, AST, ALT, GGT and ALP in the intervention group were markedly lower (P < 0.05). Furthermore, there was a markedly positive relationship between the reduction rates of body weight and GGT (P < 0.05). Conclusion: 12 weeks of aerobic exercise and dietary modiﬁcation caused signiﬁcant weight, waist circumference and body fat percentage reduction in overweight and obese men and their liver function was improved. The ﬁndings can provide a scientiﬁc reference for the improvement of liver function and prevention of liver diseases among overweight and obese people.

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Mineralocorticoids and Cardiovascular Disease in Females with Insulin Resistance and Obesity

Cited by 5 publications

References 74 publications

Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice

Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice

Using optimal subset regression to identify factors associated with insulin resistance and construct predictive models in the US adult population

Effect of a combination of aerobic exercise and dietary modiﬁcation on liver function in overweight and obese men

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