Vascular Pathways of Testosterone: Clinical Implications

Lorigo, Margarida; Mariana, Melissa; Oliveira, Nelson Fernandes de; Lemos, Manuel C.

doi:10.1007/s12265-019-09939-5

Cited by 27 publications

(21 citation statements)

References 169 publications

(279 reference statements)

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“…In addition, we also found that the level of 11-ketoetiocholanolone, an endogenous anabolic androgenic steroid, increased after GXSTC treatment. Studies have shown that lower levels of serum endogenous testosterone are associated with a higher risk of diseases such as atherosclerosis, myocardial infarction, chronic heart failure and obesity (Fink et al, 2018;Lorigo et al, 2020), and our results indicated that GXSTC also played a role in the regulation of androgen metabolism.…”

Section: Discussionsupporting

confidence: 67%

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics

Wang

Shi

et al. 2021

Front. Pharmacol.

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Background: Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy.Methods: A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis.Results: GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis.Conclusion: GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD.

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Section: Discussionsupporting

confidence: 67%

Study of the Mechanism of Action of Guanxin Shutong Capsules in the Treatment of Coronary Heart Disease Based on Metabolomics

Wang

Shi

et al. 2021

Front. Pharmacol.

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“…The following hypothesis may explain our results: the altered testosterone-induced relaxation and still unchanged nuclear AR expression may suggest the involvement of 'membrane-bound or other' receptors, signal transduction pathways, and ion channels in the identified functional damage. Additionally, it is probable that both endotheliumdependent and endothelium-independent, direct vascular smooth muscle cell activation pathways are present [18], but the exact mechanisms and the detailed cardiovascular effects of androgens are still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Sexual steroids have potential roles in cardiovascular sex-related variance; testosterone (T) and 17-β-estradiol (E2) are the two most potent sexual steroids (T in men and E2 in women), and both can cause genomic and rapid, non-genomic vasodilation via several different mechanisms and pathways, mostly in the appropriate sex [17,18].…”

Section: Introductionmentioning

confidence: 99%

“…Androgens also have nuclear and 'membrane-bound or other' receptors. Besides the classical nuclear androgen receptor (AR), numerous receptors, signal transduction pathways, and ion channels have been investigated, which may have possible roles in androgen-induced vasodilation: the PLC, G-protein coupled receptor C6A (GPRC6A), oxoeicosanoid receptor 1 (OXER1), L dual oxidase 1 (DUOX1), Zinc transporter protein 9 (ZIP9), L-type voltage-dependent calcium-channel (LVDCC), voltage-dependent potassium channel (K v ), small-and large-conductance calcium-activated potassium channels (SK Ca , BK Ca ), PI3K/Akt signaling pathway, modulation of cAMP and cGMP levels, mitochondrial procaspase 3 and 8, NADPH oxidase, and transient receptor potential cation channel family members (TRPM8, TRPV4) [18,21]. Estrogens and androgens may affect platelet functions via the sex difference that was described in the effect of antithrombotic drugs [22].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D Deficiency Reduces Vascular Reactivity of Coronary Arterioles in Male Rats

Fontányi

Sziva

Pál

et al. 2021

CIMB

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Background: Vitamin D deficiency (VDD) may be considered an independent cardiovascular (CV) risk factor, and it is well known that CV risk is higher in males. Our goal was to investigate the pharmacological reactivity and receptor expression of intramural coronary artery segments of male rats in cases of different vitamin D supply. Methods: Four-week-old male Wistar rats were divided into a control group (n = 11) with optimal vitamin D supply (300 IU/kgbw/day) and a VDD group (n = 11, <0.5 IU/kgbw/day). After 8 weeks of treatment, intramural coronary artery segments were microprepared, their pharmacological reactivity was examined by in vitro microangiometry, and their receptor expression was investigated by immunohistochemistry. Results: Thromboxane A2 (TXA2)-agonist induced reduced vasoconstriction, testosterone (T) and 17-β-estradiol (E2) relaxations were significantly decreased, a significant decrease in thromboxane receptor (TP) expression was shown, and the reduction in estrogen receptor-α (ERα) expression was on the border of significance in the VDD group. Conclusions: VD-deficient male coronary arteries showed deteriorated pharmacological reactivity to TXA2 and sexual steroids (E2, T). Insufficient vasoconstrictor capacity was accompanied by decreased TP receptor expression, and vasodilator impairments were mainly functional. The decrease in vasoconstrictor and vasodilator responses results in narrowed adaptational range of coronaries, causing inadequate coronary perfusion that might contribute to the increased CV risk in VDD.

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“…Lorigo et al summarized the association of testosterone with multiple risk factors of CVDs, such as type 2 diabetes mellitus, obesity, hypertension, and dyslipidemia. The relationship between the reduced testosterone level and the pathophysiology of vascular dysfunction, coronary arterial diseases, heart failure, ischemic stroke, and atrial fibrillation has also been discussed [5]. These papers provide a very good overview to enhance our knowledge of gender differences in CVDs.…”

mentioning

confidence: 99%