scholarly journals Aldose reductase deficiency enhances high fat diet‐induced hyper‐insulinemia and endothelial dysfunction

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Ishan Mehta ◽  
Daniel Conklin ◽  
Sanjay Srivastava ◽  
Aruni Bhatnagar
2017 ◽  
Vol 114 (2) ◽  
pp. 312-323 ◽  
Author(s):  
Sebastian Steven ◽  
Mobin Dib ◽  
Michael Hausding ◽  
Fatemeh Kashani ◽  
Matthias Oelze ◽  
...  

Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Stefanie M. Azevedo ◽  
Steve D. Menicucci ◽  
Jay S. Naik

2020 ◽  
Vol 39 (8) ◽  
pp. 1005-1018 ◽  
Author(s):  
I Cinar ◽  
Z Halici ◽  
B Dincer ◽  
B Sirin ◽  
E Cadirci

The presence of 5-HT7r’s in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r’s, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r’s by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r’s are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.


2012 ◽  
Vol 17 (6) ◽  
pp. 416-423 ◽  
Author(s):  
Po Chen ◽  
Ke Xia ◽  
Zhenyu Zhao ◽  
Xu Deng ◽  
Tianlun Yang

2018 ◽  
Vol 36 (3) ◽  
pp. 162-169 ◽  
Author(s):  
Danchun Lan ◽  
Nenggui Xu ◽  
Jian Sun ◽  
Zhixing Li ◽  
Rongzhen Liao ◽  
...  

Objective To investigate the effect of electroacupuncture (EA) on endothelial dysfunction related to high fat diet (HFD)-induced insulin resistance through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. Methods Twenty-four male Sprague-Dawley rats were fed a regular diet (Control group, n=8) or a HFD (n=16) for 12 weeks to induce an insulin resistance model. HFD-fed rats were divided into two groups that remained untreated (HFD group, n=8) or received electroacupuncture (HFD+EA group, n=8). EA was applied at PC6, ST36, SP6 and BL23. At the end of the experiment, fasting blood glucose (FBG), serum insulin (FINS), serum C-peptide (C-P) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were determined. Pancreatic islet samples were subjected to histopathological examination. The thoracic aorta was immunostained with anti-rat insulin receptor substrate (IRS)-1, Akt and endothelial nitric oxide synthase (eNOS) antibodies. mRNA and protein expression of IRS-1, PI3K, Akt2 and eNOS in the vascular endothelium were determined by real-time PCR and Western blot analysis, respectively. Results The bodyweight increase of the HFD+EA group was smaller than that of the untreated HFD group. Compared with the HFD group, the levels of FBG, FINS, C-P and HOMA-IR in the HFD+EA group decreased significantly (P<0.01). Histopathological evaluation indicated that EA improved pancreatic islet inflammation. The expression of endothelial markers, such as IRS-1, PI3K, Akt2 and eNOS, decreased in the HFD group, while EA treatment appeared to ameliorate the negative impact of diet. Conclusion EA may improve insulin resistance and attenuate endothelial dysfunction, and therefore could play a potential role in the prevention or treatment of diabetic complications and cardiovascular disease through the PI3K/Akt signalling pathway.


2005 ◽  
Vol 82 (4) ◽  
pp. 751-759 ◽  
Author(s):  
Qiang Shi ◽  
Jane F Vandeberg ◽  
Catherine Jett ◽  
Karen Rice ◽  
Michelle M Leland ◽  
...  

2009 ◽  
Vol 15 (S3) ◽  
pp. 21-22 ◽  
Author(s):  
I. Tomada ◽  
N. Tomada ◽  
H. Almeida ◽  
P. Vendeira ◽  
D. Neves

AbstractErectile dysfunction (ED) is considered equivalent to endothelial dysfunction and thus an early manifestation of atherosclerosis and cardiovascular disease (CVD). Atherosclerosis that is frequently provoked by regular consumption of high-fat diet (HFD) has been recently recognized as a chronic inflammation condition associated to vessel lipid deposition and vascular smooth cells proliferation that together impair endothelium-dependent relaxation of corpus cavernosum (CC) smooth muscle. It is also well established that HFD regular intake by its own induces endothelial dysfunction. The main objective of this study was to evaluate effects of HFD continuous intake on atherosclerosis progression of CC vessels of the rat. Due to their intervention on atherosclerosisrelated vascular remodelling pathways, angiopoietins (Ang1, Ang2) expression in erectile tissue of this rat experimental model was characterized.


Lipids ◽  
2000 ◽  
Vol 35 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Ada M. Cuevas ◽  
Viviana Guasch ◽  
Oscar Castillo ◽  
Veronica Irribarra ◽  
Claudio Mizon ◽  
...  

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