Local formation of angiotensin peptides with paracrine activity by adipocytes

Weiland, Felix; Verspohl, Eugen J.

doi:10.1002/psc.1174

Cited by 18 publications

(12 citation statements)

References 42 publications

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“…In addition to MR and GR, AT 1 R seems to be important for ACM effects, because candesartan attenuated ACM-mediated VSMC signaling. Together with aldosterone and corticosterone, we detected Ang II in ACM, supporting a role for adipocyte-derived Ang II in the activation of VSMC AT 1 R. 21 It is also possible that Ang II/AT 1 R interacts directly with MR in VSMCs and/or that AT 1 Rs are activated in a ligand-independent manner, as demonstrated previously. [22][23][24] MRs and GRs belong to the nuclear receptor superfamily and share high sequence homology.…”

Section: Discussionsupporting

confidence: 87%

Adipocyte-Derived Factors Regulate Vascular Smooth Muscle Cells Through Mineralocorticoid and Glucocorticoid Receptors

et al. 2011

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Abstract-Adipose tissue influences vascular function through adipocyte-derived factors, including components of the renin-angiotensin-aldosterone system. Molecular mechanisms underlying these phenomena are elusive. We investigated the role of adipocyte-derived factors on mitogen-activated protein kinases (MAPKs), proinflammatory status, apoptosis, and mitogenic signaling in vascular smooth muscle cells (VSMCs) and questioned whether these effects involve mineralocorticoid receptor (MR), glucocorticoid receptor (GR), and angiotensin II type 1 receptor (AT 1 R). Cultured mouse VSMCs were exposed to adipocyte-conditioned medium (ACM) from differentiated 3T3-L1 adipocytes. ACM induced phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase, p38MAPK, and extracellular signal-regulated kinase 1/2 and increased expression of proinflammatory and proliferative markers in VSMCs. Eplerenone (MR antagonist), mifepristone (GR antagonist), and candesartan (AT 1 R antagonist) inhibited ACM-induced effects on extracellular signal-regulated kinase 1/2, p38MAPK, and proliferating cell nuclear antigen, without influencing apoptosis (Bax, Bcl, and caspase 3). Stress-activated protein kinase/c-Jun N-terminal kinase phosphorylation was inhibited by mifepristone and candesartan but not by eplerenone. ACM-induced increase of fibronectin, vascular cell adhesion molecule 1, and plasminogen activator inhibitor 1 expression was blocked by MR and AT 1 R antagonism but not by GR inhibition. ACM has no effect on GR, MR, and AT 1 R expression. Our data show that adipocyte-derived factors influence MAPK signaling, leading to VSMC proinflammatory and profibrotic responses through distinct pathways. Although ACM stimulates p38MAPK and extracellular signal-regulated kinase 1/2 phosphorylation through MR, GR, and AT 1 R, activation of stress-activated protein kinase/c-Jun N-terminal kinase involves GR and AT 1 R. These findings suggest that adipocyte-derived factors regulate VSMC function through specific MAPKs linked to MR, GR, and AT 1 R, a posttranslational phenomenon, because ACM did not influence receptor expression. Such cross-talk between adipocytes and VSMCs may provide a potential molecular mechanism linking renin-angiotensin-aldosterone system, adipocytes, and vascular function.

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Section: Discussionsupporting

confidence: 87%

Adipocyte-Derived Factors Regulate Vascular Smooth Muscle Cells Through Mineralocorticoid and Glucocorticoid Receptors

et al. 2011

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“…Adipocytes have all components of the renin-angiotensin system and thus produce locally generated angiotensin II. 50-52 A growing body of evidence suggests that adipocytes produce and release factors, that may stimulate aldosterone release independent of renin-angiotensin. 53, 54, 55-58,59 Ehrhart-Bornstein et al have provided evidence of adipocyte secretory products that directly stimulate adrenocortical aldosterone secretion.…”

Section: Discussionmentioning

confidence: 99%

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Dudenbostel¹,

Ghazi²,

Liu³

et al. 2016

Hypertension

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Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension (RHTN). A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with RHTN has not been previously investigated. Our objective was to determine if BMI is positively correlated with plasma aldosterone concentration (PAC), plasma renin activity (PRA), aldosterone-renin ratio (ARR), and 24-hour urinary aldosterone (24-hr UAldo) African-American (AA) and Caucasian patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with RHTN. The relation between PAC, PRA, ARR, 24-hr UAldo and BMI was investigated for the entire cohort, by gender, and race (65.3% Caucasian, 40.3% men). We demonstrate that PAC and ARR were significantly correlated to BMI (p<0.0001) across the first three quartiles, but not from the 3rd to 4th quartile of BMI. PRA was not correlated with BMI. 24-hr UAldo was positively correlated across all quartiles of BMI for the cohort (p<0.0001) and when analyzed by gender (men p<0.0001; women p=0.0013) and race (p<0.05), and stronger for men compared to women (r=0.19, p<0.001 versus r=0.05, p=0.431, p=0.028) regardless of race. In both AA and Caucasian patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in AA and Caucasian men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with RHTN.

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“…Mas receptor stimulates adipogenesis via the PI3K pathway (175). Its specific agonist, ANG 1-7, is the main product found in supernatants of 3T3-L1 adipocytes exposed to ANG I (187). ANG II promotes the local synthesis of prostacyclin in adipocytes, which is a potent adipogenic factor (150).…”

Section: Raas Modulates Adipogenesis Lipogenesis and Wat Content Ofmentioning

confidence: 99%

Modulation of glucose metabolism by the renin-angiotensin-aldosterone system

Favrè

Esnault

Obberghen

2015

American Journal of Physiology-Endocrinology and Metabolism

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The renin-angiotensin-aldosterone system (RAAS) is an enzymatic cascade functioning in a paracrine and autocrine fashion. In animals and humans, RAAS intrinsic to tissues modulates food intake, metabolic rate, adiposity, insulin sensitivity, and insulin secretion. A large array of observations shows that dysregulation of RAAS in the metabolic syndrome favors type 2 diabetes. Remarkably, angiotensin-converting enzyme inhibitors, suppressing the synthesis of angiotensin II (ANG II), and angiotensin receptor blockers, targeting the ANG II type 1 receptor, prevent diabetes in patients with hypertensive or ischemic cardiopathy. These drugs interrupt the negative feedback loop of ANG II on the RAAS cascade, which results in increased production of angiotensins. In addition, they change the tissue expression of RAAS components. Therefore, the concept of a dual axis of RAAS regarding glucose homeostasis has emerged. The RAAS deleterious axis increases the production of inflammatory cytokines and raises oxidative stress, exacerbating the insulin resistance and decreasing insulin secretion. The beneficial axis promotes adipogenesis, blocks the production of inflammatory cytokines, and lowers oxidative stress, thereby improving insulin sensitivity and secretion. Currently, drugs targeting RAAS are not given for the purpose of preventing diabetes in humans. However, we anticipate that in the near future the discovery of novel means to modulate the RAAS beneficial axis will result in a decisive therapeutic breakthrough.

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Local formation of angiotensin peptides with paracrine activity by adipocytes

Cited by 18 publications

References 42 publications

Adipocyte-Derived Factors Regulate Vascular Smooth Muscle Cells Through Mineralocorticoid and Glucocorticoid Receptors

Adipocyte-Derived Factors Regulate Vascular Smooth Muscle Cells Through Mineralocorticoid and Glucocorticoid Receptors

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Modulation of glucose metabolism by the renin-angiotensin-aldosterone system

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