Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor Β1 and urinary albumin excretion

Scaglione, Rosario; Argano, Christiano; Chiara, Tiziana Di; Colomba, Daniela; Parrinello, Giovanni; Corrao, Salvatore; Avellone, G; Licata, Giuseppe

doi:10.1080/08037050310016484

Cited by 34 publications

(30 citation statements)

References 17 publications

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“…In humans, the circulating levels of TGF-β 1 , a homodimer composed of two 12.5-kDa subunits, correlate positively with the body mass index (BMI) [98]. This correlation also exists between the BMI and TGF-β 1 production in WAT, a feature that holds especially for the vis WAT that produces more than two-fold more TGF-β 1 compared to the sc WAT in humans [99,100].…”

Section: Adipokines Chemokines and Vascular Proteins Involved In Prmentioning

confidence: 66%

Fat poetry: a kingdom for PPARγ

2007

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Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor g (PPARg), which is a fatty acid-and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARg agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARg in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARg modulators.

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Section: Adipokines Chemokines and Vascular Proteins Involved In Prmentioning

confidence: 66%

Fat poetry: a kingdom for PPARγ

2007

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“…TGFb1 levels were determined by using a solid-phase-specific sandwich (R&D Systems Inc., Minneapolis, USA) ELISA technique as previously described. 17,18,24 The interassay and intraassay variations for determining TGFb1 were 8 and 6%, respectively. The sensitivity, hence, minimum level of detection of TGFb1 by sandwich ELISA, was 5 pg/ml.…”

Section: Tgfb1mentioning

confidence: 99%

“…In fact, circulating TGFb1 overproduction has been reported in hypertensive subjects, central obeses and related to the target-organ disease. 17,18,31 A genetic TGFb1 DNA polimorphysm, 32 angiotensin II activity 33 and shear stress 34 have been proposed to explain TGFb1 overproduction in obesity-associated hypertension.…”

Section: Left Ventricular Filling Abnormalities and Obesity-associatementioning

confidence: 99%

“…Patients with microalbuminuria and proteinuria were also excluded since a TGFb1 overproduction has been reported in these conditions. [16][17][18] An accurate diagnostic procedure was performed in all the subjects with suspected coronary heart disease. This includes basal and 24 h ECG, echocardiography and, where necessary, ECG after exercise.…”

Section: Patientsmentioning

confidence: 99%

“…[13][14][15] Overproduction of TGFb1 is involved in obesityassociated hypertension and in the long-term sequelae of hypertension, including LVH, vascular remodelling and progressive renal disease. [16][17][18] Moreover, some recent data suggest that TGFb1 might play a casual role in myocardial fibrosis and diastolic dysfunction both in pressure overload hearts 19 and after heart transplantation. 20 In addition, the blocking of TGFb1 with monoclonal antibodies has been reported to be effective to neutralize myocardial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor β1

et al. 2005

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This study has been designed to evaluate the relationship among transforming growth factor b1 (TGFb1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFb1 and M-and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricular hypertrophy (LVH) was determined in all the groups. TGFb1, left ventricular mass (LVM), LVM/h 2.7 , E-wave deceleration time and isovolumic relaxation time (IVRT) were significantly (Po0.005) higher and E/A velocity ratio was significantly (Po0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH was significantly higher (Po0.03) in group OB-HT than in L-HT. TGFb1 (Po0.004), LVM/h 2.7 (Po0.001) and prevalence of LVH were (Po0.01) significantly higher in hypertensives with diastolic dysfunction than hypertensives with normal diastolic function. TGFb1 levels were positively correlated with BMI (r ¼ 0.60; Po0.0001), LVM/h 2.7 (r ¼ 0.28; Po0.03), IVRT (r ¼ 0.30; Po0.02) and negatively with E/A ratio (r ¼ À0.38; Po0.002) in all HT. Multiple regression analysis indicated that TGFb1, BMI and IVRT were independently related to E/A ratio explaining 71% of its variability (r ¼ 0.84; Po0.0001). This relationship was independent of LVH, age and HR suggesting that TGFb1 overproduction may be considered a pathophysiological mechanism in the development of left ventricular filling abnormalities in obesity-associated hypertension.

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Smad-independent pathway involved in transforming growth factor β1-induced Nox4 expression and proliferation of endothelial cells

Hakami

Wong

Shah

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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NADPH oxidase-derived reactive oxygen species are important for various cellular functions, including proliferation. Endothelial cells predominantly express the Nox4 isoform of NADPH oxidase, but it is not entirely clear how it is regulated. In this study, we investigated the signalling pathways involved in transforming growth factor-β1 (TGF-β1)-induced Nox4 expression and the proliferation of human microvascular endothelial cells (HMECs). TGF-β1 stimulated Nox4 messenger RNA and protein expression in HMECs. TGF-β1-induced Nox4 also increased hydrogen peroxide production, which was inhibited by diphenyleneiodonium and EUK134. The acute treatment of HMECs with TGF-β1 enhanced the phosphorylation of Smad2 and extracellular signal-regulated kinase (ERK) 1/2, without affecting p38MAPK, Akt, or Jun N-terminal kinase 1/2 (JNK1/2) pathways. Further, inhibition of Smad2 signalling using an inhibitor of activin receptor-linked kinase 5 SB431542 reduced TGF-β1-induced Nox4 expression, while inhibition of ERK1/2 with the inhibitor of mitogen-activated protein kinase kinase 1/2 U0126 decreased both basal and TGF-β1-induced Nox4 expression. Inhibition of ERK1/2 phosphorylation with U0126 did not affect Smad2 phosphorylation. Finally, TGF-β1 enhanced endothelial cell proliferation, which was reduced by U0126 but not by SB431542. These findings suggest that the non-canonical pathway ERK1/2 regulates Nox4 expression and may be involved in TGF-β1-induced proliferation of endothelial cells, which is vital during angiogenesis and vascular development.

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Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor Β1 and urinary albumin excretion

Abstract: Our data suggest that TGFbeta1 levels are positively associated with BMI, MBP and UAE in hypertensive subjects. This also indicates that TGFbeta1 overproduction might be considered a pathophysiology mechanism of progressive renal function impairment in obese hypertensives.

Cited by 34 publications

References 17 publications

Fat poetry: a kingdom for PPARγ

Fat poetry: a kingdom for PPARγ

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor β1

Smad-independent pathway involved in transforming growth factor β1-induced Nox4 expression and proliferation of endothelial cells

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