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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic syndrome is a highly predisposing condition for cardiovascular disease and could be a cause of excess salt-induced organ damage. Recently, several investigators have demonstrated that salt loading causes left ventricular diastolic dysfunction associated with increased oxidative stress and mineralocorticoid receptor activation. We, therefore, investigated whether excess salt induces cardiac diastolic dysfunction in metabolic syndrome via increased oxidative stress and upregulation of mineralocorticoid receptor signals. Thirteen-week-old spontaneously hypertensive rats and SHR/NDmcr-cps, the genetic model of metabolic syndrome, were fed a normal salt (0.5% NaCl) or high-salt (8% NaCl) diet for 4 weeks. In SHR/NDmcr-cps, salt loading induced severe hypertension, abnormal left ventricular relaxation, and perivascular fibrosis. Salt-loaded SHR/NDmcr-cps also exhibited overproduction of reactive oxygen species and upregulation of mineralocorticoid receptor-dependent gene expression, such as Na(+)/H(+) exchanger-1 and serum- and glucocorticoid-inducible kinase-1 in the cardiac tissue. However, in spontaneously hypertensive rats, salt loading did not cause these cardiac abnormalities despite a similar increase in blood pressure. An antioxidant, tempol, prevented salt-induced diastolic dysfunction, perivascular fibrosis, and upregulation of mineralocorticoid receptor signals in SHR/NDmcr-cps. Moreover, a selective mineralocorticoid receptor antagonist, eplerenone, prevented not only diastolic dysfunction but also overproduction of reactive oxygen species in salt-loaded SHR/NDmcr-cps. These results suggest that metabolic syndrome is a predisposed condition for salt-induced left ventricular diastolic dysfunction, possibly via increased oxidative stress and enhanced mineralocorticoid receptor signals.
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PMID:Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder. 1860 4

Aldosterone is an adrenal hormone that regulates sodium, fluid, and potassium balance. Jerome Conn first described the syndrome of autonomous and excessive aldosterone secretion or "primary aldosteronism." Contrary to the historical belief, recent studies indicate that primary aldosteronism is a common cause of hypertension with a prevalence of 5-10% among general hypertensive patients. Various animal models have demonstrated that aldosterone in association with a high salt diet results in target-organ inflammation and fibrosis. Similarly, cross-sectional and observational human studies have demonstrated the association of aldosterone with development and severity of hypertension, congestive heart failure, coronary artery disease, chronic kidney disease, and metabolic syndrome. Several interventional studies have also demonstrated the beneficial effects of mineralocorticoid receptor antagonists in these disease processes, particularly hypertension, heart failure, and post myocardial infarction, further supporting the role of aldosterone in their pathogenesis. We review the role of aldosterone in these various cardiovascular disease processes along with potential mechanisms and treatment.
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PMID:Aldosterone and cardiovascular disease. 1913 16

Primary aldosteronism is the most common cause of secondary hypertension, accounting for about 10% of all forms of high blood pressure. Life-time pharmacological therapy is the treatment of choice for primary aldosteronism due to idiopathic adrenal hyperplasia (IHA), while adrenalectomy is effective in curing most patients with an aldosterone producing adenoma (APA). Far from being a benign form of hypertension, primary aldosteronism is characterized by the development of cardiovascular renal and metabolic complications, including left ventricular hypertrophy, myocardial infarction, atrial fibrillation and stroke, microalbuminuria, renal cysts as well as metabolic syndrome, glucose impairment and diabetes mellitus. We review recent clinical experience with the above mentioned complications and long-term outcomes of blood pressure normalization and cardiac, renal and gluco-metabolic complications in patients with primary aldosteronism, after medical treatment with mineralocorticoid receptor antagonists and surgical treatment. We conclude that removal of adrenal adenoma results in normalization of the renin-angiotensin-aldosterone system (RAAS) and of kalaemia and improvement of blood pressure levels in all patients. Complete resolution of hypertension is achieved in nearly half of treated patients. Moreover, unilateral adrenalectomy is the best treatment to have the regression of cardiovascular, renal and metabolic complications in patients with APA. On the other hand, targeted medical treatment with aldosterone antagonists improves blood pressure control and appears able to prevent the progression of cardiac and metabolic complications in patients with IHA.
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PMID:Management of primary aldosteronism: its complications and their outcomes after treatment. 1935 5

Certain patient populations have a high prevalence of hypertension, including black, elderly, or obese patients; patients with metabolic syndrome, or frank diabetes; and patients with chronic kidney disease. Many of these patients experience renin-angiotensin-aldosterone system (RAAS) dysregulation, which is important because the RAAS plays a pivotal role in the pathogenesis of hypertension, cardiovascular disease, and renal dysfunction. Data available regarding newer approaches that target the RAAS, including direct renin inhibition and aldosterone receptor antagonism, in patients who often have hypertension are reviewed. Aliskiren, the first direct renin inhibitor, is effective in a number of these patient groups, including those who are black or obese or who have metabolic syndrome, renal impairment, or diabetes. In addition, in the setting of long-term angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, aldosterone receptor antagonists (spironolactone and eplerenone) provide another rational therapeutic approach for patients whose blood pressure is not controlled by standard therapies.
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PMID:New therapeutic options in patients prone to hypertension: a focus on direct Renin inhibition and aldosterone blockade. 1939 Apr 29

The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin-angiotensin-aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic beta-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease.
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PMID:Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. 1948 12

Obesity hypertension and metabolic syndrome have become major public health concerns. Nowadays, aldosterone is recognized as an important mediator of cardiovascular and renal damage. In the kidney, aldosterone injures glomerular visceral epithelial cells (podocytes), the final filtration barrier to plasma macromolecules, leading to proteinuria and glomerulosclerosis. Mineralocorticoid receptor (MR) antagonists effectively ameliorate proteinuria in patients or in animal models of hypertension, diabetes mellitus and chronic kidney disease (CKD), as well as in patients who experience 'aldosterone breakthrough.' Recently, clinical and experimental studies have shown that plasma aldosterone concentration is associated with obesity hypertension and metabolic syndrome. We showed that spontaneously hypertensive rats (SHR)/cp, an experimental model of obesity hypertension and metabolic syndrome, are prone to glomerular podocyte injury, proteinuria and left ventricular diastolic dysfunction, especially when the animals are fed a high-salt diet. Inappropriate activation of the aldosterone/MR system underlies the renal and cardiac injuries. Adipocyte-derived aldosterone-releasing factors (ARFs), although still unidentified, may account for aldosterone excess and the resultant target organ complication in SHR/cp. On the other hand, recent studies have shown that MR activation triggers target organ disease even in normal or low aldosterone states. We identified a small GTP (guanosine triphosphate)-binding protein, Rac1, as a novel activator of MR, and showed that this ligand-independent MR activation by Rac1 contributes to the nephropathy of several CKD models. We expect that ARFs and Rac1 can be novel therapeutic targets for metabolic syndrome and CKD. Future large-scale clinical trials are awaited to prove the efficacy of MR blockade in patients with obesity hypertension and metabolic syndrome.
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PMID:Mineralocorticoid receptor activation in obesity hypertension. 1952 18

The mineralocorticoid receptor (MR) mediates aldosterone effects on salt homeostasis and blood pressure regulation. MR activation also promotes inflammation, cardiovascular remodelling and endothelial dysfunction, and affects adipose tissue differentiation and function. Some of these effects derive from MR activation by glucocorticoids. Recent epidemiological studies show that the incidence of metabolic syndrome increases across quartiles of aldosterone, implicating the MR as a central player in metabolic homeostasis, involving electrolyte, water and energy balance. This review summarizes the current understanding of MR-mediated effects in diverse tissues and the role of aldosterone as a cardiometabolic risk factor, and discusses the possible relationship between inappropriate MR activation (by both mineralocorticoids and glucocorticoids) and the development of metabolic syndrome.
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PMID:Mineralocorticoid receptors in the metabolic syndrome. 1980 Feb 55

Obesity is associated with chronic inflammation. Pro-inflammatory adipokines may promote metabolic disorders and cardiovascular morbidity. However, the key mechanisms leading to obesity-related inflammation are poorly understood. The corticosteroid metabolism in adipose tissue plays a crucial role in the pathogenesis of the metabolic syndrome. Both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) mediate corticosteroid action in adipose tissue. The significance of the interplay of these receptors in mediating an inflammatory adipokine response is virtually unexplored. In the present study, we investigated the differential roles of the GR and MR in controlling the key adipose tissue functions including inflammatory adipokine expression and adipogenesis using selective stimulation with receptor agonists, acute receptor knockdown via RNA interference and newly generated knockout adipose cell lines. Selective GR stimulation of white adipocytes with dexamethasone inhibited the expression of interleukin 6 (IL6), monocyte chemoattractant protein-1 (MCP1 or CCL2 as listed in the MGI Database), tumour necrosis factor-alpha, chemerin and leptin. By contrast, selective MR stimulation with aldosterone promoted the expression of IL6, plasminogen activator inhibitor 1, chemerin and leptin. Furthermore, in the presence of an acute GR knockdown as well as in GR knockout adipocytes, corticosterone increased the gene expression of the pro-inflammatory adipokines IL6 and MCP1. Whereas GR knockout adipocytes displayed a mildly impaired adipogenesis during early differentiation, MR knockout cells completely failed to accumulate lipids. Taken together, our data demonstrate a critical role for the balance between gluco- and mineralocorticoid action in determining adipocyte responses implicated in obesity-associated inflammation and cardiovascular complications.
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PMID:The balance between gluco- and mineralo-corticoid action critically determines inflammatory adipocyte responses. 1993 12

The role of aldosterone has been implicated in the metabolic syndrome and cardiovascular diseases. The biological actions of aldosterone are mediated through mineralocorticoid receptor (MR). Nuclear receptor-mediated gene expression is regulated by dynamic and coordinated recruitment of coactivators and corepressors. To identify new coregulators of the MR, full-length MR was used as bait in yeast two-hybrid screening. We isolated NF-YC, one of the subunits of heterotrimeric transcription factor NF-Y. Specific interaction between MR and NF-YC was confirmed by yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation assays, and fluorescence subcellular imaging. Transient transfection experiments in COS-7 cells demonstrated that NF-YC repressed MR transactivation in a hormone-sensitive manner. Moreover, reduction of NF-YC protein levels by small interfering RNA potentiated hormonal activation of endogenous target genes in stably MR-expressing cells, indicating that NF-YC functions as an agonist-dependent MR corepressor. The corepressor function of NF-YC is selective for MR, because overexpression of NF-YC did not affect transcriptional activity mediated by androgen, progesterone, or glucocorticoid receptors. Chromatin immunoprecipitation experiments showed that endogenous MR and steroid receptor coactivator-1 were recruited to an endogenous ENaC gene promoter in a largely aldosterone-dependent manner, and endogenous NF-YC was sequentially recruited to the same element. Immunohistochemistry showed that endogenous MR and NF-YC were colocalized within the mouse kidney. Although aldosterone induces interaction of the N and C termini of MR, NF-YC inhibited the N/C interaction. These findings indicate that NF-YC functions as a new corepressor of agonist-bound MR via alteration of aldosterone-induced MR conformation.
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PMID:NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor. 2005 1

Obese persons with metabolic syndrome often have associated with salt-sensitive hypertension, microalbuminuria, and cardiac dysfunction, and the plasma aldosterone level in one-third of metabolic syndrome patients is clearly elevated. Hyperaldosteronism, which may be caused at least partially by certain adipocyte-derived factors, contributes to the development of proteinuria in obese hypertensive rats, and salt loading aggravates the proteinuria and induces cardiac diastolic dysfunction because of inadequate suppression of plasma aldosterone level. However, mineralocorticoid receptor (MR) antagonists prevent salt-induced renal and cardiac damage, suggesting that aldosterone excess and a high-salt diet exert an unfavorable synergistic action on the kidney and heart. In Dahl salt-sensitive rats, however, despite appropriate suppression of plasma aldosterone with a high-salt diet, salt loading paradoxically activated renal MR signaling, and the renal injury was markedly prevented by MR antagonists. Accordingly, we discovered an alternative pathway of MR activation in which Rac1, a small GTP-binding protein, activates MRs. Salt loading activates renal Rac1 in Dahl salt-sensitive rats, and Rac1 in turn induces MR activation, which results in renal injury, and the renal injury has been found to be prevented by Rac1 inhibitors. Moreover, several metabolic syndrome-related factors induce Rac1 activation, and one of them, hyperglycemia, activates MRs via Rac1 activation. Consistent with this, Rac1 inhibitors attenuated the proteinuria and renal injury in obese hypertensive animals. Thus, both salt and obesity activate Rac1 and cause MR activation. Abnormal activation of the aldosterone/MR pathway plays a key role in the development of salt-sensitive hypertension and renal injury in metabolic syndrome.
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PMID:Mineralocorticoid receptors, salt-sensitive hypertension, and metabolic syndrome. 2017 94


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