scholarly journals N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

2020 ◽  
Author(s):  
Azza salaheldien Abdelhaffez ◽  
Ebtihal Anwar Abd El-Aziz ◽  
Maha Baghdady Tohamy ◽  
Asmaa Mahmoud Ahmed
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Protective Effect ◽  
Body Weight Gain ◽  
Cardiovascular Effects ◽  
Heart Weight ◽  
High Density Lipoproteins ◽  
Down Regulation ◽  
Myocardial Degeneration ◽  
Acetyl Cysteine

Abstract Background Chronic fructose consumption is associated with development of obesity, insulin resistance (IR) and metabolic syndrome (MS). Cardiovascular diseases are linked to metabolic deregulation observed in MS. N-acetylcysteine (NAC) is a sulfur containing compound of Allium plants (such as garlic and onion) that increases intracellular reduced glutathione concentrations, which is an endogenous antioxidant. Methods This study investigated the ability of N-acetyl cysteine (NAC) to alleviate the metabolic disorders in fructose-induced MS in male Wistar rats and to examine its protective effect on aortic and cardiac tissues via its influence on cardiotrophin-1 (CT-1) expression. NAC (20 mg/kg b.w./day) was administered to fructose (20% w/v) induced MS animals for twelve weeks. Results Chronic fructose consumption increased body weight gain, relative heart weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), IR and associated with metabolic alterations. Histological and immunohistochemical examination revealed aortic stiffness and myocardial degeneration and fibrosis together with increased CT-1 expression. Treatment with NAC improved IR, SBP, DBP and mitigated atherogenic dyslipidaemia and oxidative stress (OS). Additionally, NAC down-regulated CT-1 expression in the heart and aorta. Furthermore, CT-1 expression in the heart and aorta was positively correlated with basal glycemia, final SBP and DBP, total cholesterol, triglycerides, low density lipoproteins and negatively correlated with high density lipoproteins levels. Conclusion The findings reported here demonstrated, for the first time, the protective effect of NAC against aortic and myocardial degeneration and fibrosis through down-regulation of CT-1 in fructose induced MS animal model. Also, our results revealed the infallible role of NAC to blunt the cardiometabolic deregulation observed in MS.

scholarly journals The prevalence of metabolic syndrome in male patients of early onset androgenic alopecia compared to age matched controls

2021 ◽  
Author(s):  
Nitin D. Chaudhari ◽  
Chandrakant B. Poulkar ◽  
Swapna S. Khatu ◽  
Gaurav H. Khandait ◽  
Rajvardhan M. Bagane ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Early Onset ◽  
High Density ◽  
High Density Lipoproteins ◽  
P Value ◽  
Early Screening ◽  
Androgenic Alopecia ◽  
Male Patients

<p class="abstract"><strong>Background:</strong> Androgenic alopecia is most common type of non-scarring alopecia in men. It is associated with high risk of cardiovascular events. Aim was to study the prevalence of metabolic syndrome in male patients of early onset androgenic alopecia.</p><p class="abstract"><strong>Methods:</strong> A case-control study was conducted at the dermatology out-patient department over a period of 6 months which included 100 patients of androgenic alopecia and 100 age matched controls. All subjects were aged 20 to 35 years and underwent detailed history, clinical examination including trichoscopic examination and measurement of waist circumference and blood pressure. Fasting blood sugar, triglyceride and high-density lipoproteins were tested following overnight fasting. Diagnosis of metabolic syndrome was based on criteria of national cholesterol education program (NCEP) adult treatment panel III. Chi square test was used as a test of significance. P value &lt;0.05 was considered statistically significant.<strong></strong></p><p class="abstract"><strong>Results:</strong> Prevalence of metabolic syndrome was more in androgenic alopecia patients than in controls (48% versus 18%, p value &lt;0.001). Androgenic alopecia patients had higher prevalence of increased waist circumference (76% versus 28%, p value &lt;0.0001), increased diastolic blood pressure (32% versus 12%, p value=0.007), increased serum triglycerides (46% versus 24%, p value=0.0011) and decreased serum high-density lipoproteins (36% versus 18%, p value=0.0042) compared to controls.</p><p class="abstract"><strong>Conclusions:</strong> Early screening for metabolic syndrome and its components is beneficial in patients with androgenic alopecia to reduce cardiovascular mortality.</p>

scholarly journals Associations between metabolic syndrome and reduced lung function in young people

2017 ◽  
Vol 89 (10) ◽  
pp. 54-61
Author(s):  
N A Kovalkova ◽  
Yu I Ragino ◽  
N Yu Travnikova ◽  
D V Denisova ◽  
L V Shcherbakova ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Lung Function ◽  
Respiratory Function ◽  
Hdl Cholesterol ◽  
Research Society ◽  
High Density Lipoproteins ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Russian Research

Aim. To reveal possible associations between metabolic syndrome (MS) and reduced lung function. Subjects and methods. In 2013—016, a cross-sectional survey was conducted in 908 Novosibirsk dwellers, which included spirometry to evaluate external respiratory function (ERF). For the detection of MS, the investigators used the 2009 All-Russian Research Society of Cardiologists criteria: waist circumference (WC) > 80 cm for women and >94 cm for men in combination with two of the following criteria: blood pressure (BP) ≥130/85 mm Hg, triglycerides (TG) ≥1.7 mmol/l, high-density lipoproteins (HDL) cholesterol

Abstract P151: Cardiovascular Effects Of Peritoneal Dialysis In The 5/6 Nephrectomy Rat Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Victoria Nasci ◽  
Alison J Kriegel
Keyword(s):  
Blood Pressure ◽  
Peritoneal Dialysis ◽  
Statistical Significance ◽  
Cardiovascular Effects ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Home Dialysis ◽  
Post Surgery ◽  
Stage Renal Disease ◽  
End Stage

In the US more than 130,000 people are diagnosed with end stage renal disease (ESRD) each year. Of those only 3% receive a kidney transplant while the remaining 97% are reliant on dialysis for survival. Among dialysis patients, cardiovascular (CV) related events are the leading cause of death. Despite therapeutic advancements the continued CVD following the onset of dialysis poses an interesting clinical challenge that necessitates studies into the effects and effectiveness of dialysis. Furthermore, home dialysis, particularly peritoneal dialysis (PD), has been utilized increasingly in ESRD care (up 10% in 2018) thus the need to understand PD effects on the CV system is urgent. Based on clinical outcomes, we hypothesized that PD would have no effect on CV outcomes in chronic kidney disease (CKD). To study CKD, we performed 5/6 nephrectomy (5/6Nx) or sham surgery, on 10 week old male Sprague-Dawley rats. Peritoneal catheters were then implanted 6 weeks post-surgery and PD was initiated 2 days later in some of the 5/6Nx and sham animals (15ml [Baxter PD-2 2.5%] 1-hour dwell 3x/day for 9 days). Echocardiography was performed at baseline, 6-, and 7-weeks post-surgery. At week 7 pressure volume analysis was performed prior to serum and tissue collection. Statistical significance was determined by two-way ANOVA. 5/6Nx increased heart weight (5/6Nx 0.43±0.02 vs. Sham 0.34±0.01; p<0.05). PD had no effect on heart weight in sham rats, but attenuated the increase in 5/6Nx rats (5/6Nx 0.43±0.02 vs. 5/6Nx PD 0.40±0.01; p<0.05). 5/6Nx increased systolic blood pressure (5/6Nx 133.6±5.6 vs. Sham 111.1±5.9; p<0.05). PD had no effect on blood pressure in either sham or 5/6Nx rats. 5/6Nx increased cholesterol (5/6Nx 134.9±8.3 vs. Sham 104.3±11; p<0.05), but PD attenuated the rise in cholesterol in 5/6Nx rats (5/6Nx 134.9±8.3 vs. 5/6Nx PD 115.7±9; p<0.05), and greatly increased triglycerides (5/6Nx 65.6±11 vs. 5/6Nx PD 165.5±11.9; p<0.05). CV echocardiography parameters in sham animals and in 5/6Nx were unchanged by PD. These data combined suggests that PD may have little to no effects on some CV parameters while worsening others. These findings indicate more studies focused on the CV effects of dialysis are necessary to help improve outcomes in the ESRD population.

scholarly journals The Association between Zinc and Copper Circulating Levels and Cardiometabolic Risk Factors in Adults: A Study of Qatar Biobank Data

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2729
Author(s):  
Abdelhamid Kerkadi ◽  
Dana Samir Alkudsi ◽  
Sara Hamad ◽  
Hanan Mohamed Alkeldi ◽  
Reem Salih ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Inductively Coupled Plasma ◽  
Cardiometabolic Risk ◽  
High Plasma ◽  
High Density Lipoproteins ◽  
P Value ◽  
Inductively Coupled ◽  
The Status ◽  
Low Hdl

Cardiometabolic risk (CMR) factors increase the likelihood of developing cardiovascular diseases (CVD). In Qatar, 24% of the total deaths are attributed to CVDs. Several nutritional disturbances have been linked to high risk of CVD. Many studies have discussed the effects of zinc (Zn) and copper (Cu) on CMR factors; however, evidence has been controversial. This investigated the association between CMR factors and the status of Zn and Cu, in addition to Zn/Cu ratio. A total of 575 Qatari men and women aged 18 years and older were obtained from Qatar Biobank. Plasma levels of Zn and Cu were determined using inductively coupled plasma mass spectrometry (ICP-MS). Anthropometric data and CMR factors were determined using standard methods. Adjusted associations between trace minerals and CMR were estimated by logistic regression. Partial correlation was performed to test the strength of the associations. Zn was not strongly correlated (p-value ˃ 0.01) or significantly associated with CMR factors and metabolic syndrome (MetS). Cu levels correlated positively with body mass index (BMI) (0.23; p ˂ 0.001), pulse rate (PR) (0.18; p ˂ 0.001), total cholesterol (0.13; p = 0.01), and high-density lipoproteins (HDL) (0.27; p ˂ 0.001); and negatively with diastolic blood pressure (DBP) (−0.13; p = 0.01). High plasma Cu significantly decreased the risk of metabolic syndrome (MetS) (0.121; p ˂ 0.001). Furthermore, Zn/Cu ratio positively correlated with waist circumference (0.13; p = 0.01), systolic blood pressure (0.13; p ˂ 0.01), and DBP (0.14; p ˂ 0.01); and negatively with BMI (−0.19; p ˂ 0.001), PR (−0.17; p ˂ 0.001), and HDL (−0.27; p ˂ 0.001). High Zn/Cu ratio increased the prevalence of low HDL (4.508; p ˂ 0.001) and MetS (5.570; p ˂ 0.01). These findings suggest that high plasma Cu levels are associated with a protective effect on DBP, HDL and MetS and that high plasma Zn/Cu ratio is associated with the risk of having low HDL and MetS.

scholarly journals Metabolic Syndrome Among Physicians: A Pilot Study from Chattogram, Bangladesh

2021 ◽  
Vol 20 (2) ◽  
pp. 65-68
Author(s):  
Anisul Awal ◽  
Farid Uddin Ahmed
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Fasting Blood Glucose ◽  
Preventive Health Care ◽  
Medical College Hospital ◽  
High Density Lipoproteins ◽  
College Hospital ◽  
Cross Sectional ◽  
Medical College

Background : Although the information on Metabolic Syndrome (MetS) in the general population from different parts of Bangladesh is available, the information regarding the same is scarcely available from physicians of Bangladesh. This study was aimed to assess the prevalence of MetS among physicians working at Chattogram Medical College Hospital, Bangladesh. Materials and methods : Data was collected for this cross-sectional study from 255 working physicians of Chittagong Medical College Hospital in 2018. The participants filled a structured questionnaire followed by physical and biochemical measurements including waist circumference, blood pressure, lipid profile, and fasting blood glucose. National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) defines criteria were used to identify physicians with the MetS. Results : Among 255 participants (males - 192 and females - 63), 100 (39.2%) were with MetS. Prevalence of same was higher in females (41.3%) than males (38.5%). The elderly physicians (>40 years) had a higher prevalence compared to the younger (£40 years) physicians [72 (50.3%) vs. 28 (25.0%)]. In the males, low High-Density Lipoproteins-Cholesterol (HDL-C) was the major contributor to the prevalence of MetS followed by high blood pressure. However, in females, low HDL-C and greater waist circumference contributed the maximum to MetS. Conclusion : This study showed a high prevalence of MetS among physicians of Bangladesh, and thereby warrants the urgent implementation of preventive health care strategies to reduce both morbidity and mortality related to this medical problem. Further studies ought to focus on the working conditions and lifestyles of individuals in these high-risk groups. Chatt Maa Shi Hosp Med Coll J; Vol.20 (2); July 2021; Page 65-68

scholarly journals A G-protein-biased S1P1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

2021 ◽  
Author(s):  
Maria Francesca Evaristi ◽  
Bruno Poirier ◽  
Xavier Chénedé ◽  
Anne-Marie Lefebvre ◽  
Alain Roccon ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
G Protein ◽  
Rat Model ◽  
Left Ventricular ◽  
Heart Weight ◽  
Functional Components

Aim: Heart failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide with no approved treatment. Left ventricular hypertrophy (LVH) and diastolic dysfunction represent the structural and functional components of HFpEF, respectively . Endothelial dysfunction is prevalent in HFpEF and predicts cardiovascular events. We investigated if SAR247799, a G-protein-biased sphingosine-1-phosphate receptor 1 (S1P 1 ) agonist with endothelial-protective properties, could improve cardiac and renal functions in a rat model of metabolic syndrome LVH and diastolic function. Methods: 31- and 65-week-old obese ZSF1 (Ob-ZSF1) rats, representing young and old animals with LVH and diastolic dysfunction, were randomized to a chow diet containing 0.025% (w/w) of SAR247799, or control (CTRL) chow for 4 weeks. Age-matched lean ZSF1 (Le-ZSF1) rats were fed control chow. Echocardiography, telemetry, biochemical and histological analysis were performed to evaluate the effect of SAR247799. Results: Echocardiography revealed that Ob-ZSF1 rats, in contrast to Le-ZSF1 rats, developed progressive diastolic dysfunction and cardiac hypertrophy with age. SAR247799 blunted the progression of diastolic dysfunction in young and old animals: in young animals E/e’ was evaluated at 21.8 ± 1.4 for Ob-ZSF1-CTRL, 19.5 ± 1.2 for Ob-ZSF1-SAR247799 p<0.01, and 19.5 ± 2.3 for Le-ZSF1-CTRL (median ± IQR). In old animals E/e’ was evaluated at 23.15 ± 4.45 for Ob-ZSF1-CTRL, 19.5 ± 5 for Ob-ZSF1-SAR247799 p<0.01, and 16.69 ± 1.7 for Le-ZSF1-CTRL, p<0.01 (median ± IQR). In old animals, SAR247799 reduced cardiac hypertrophy (mean ± SEM of heart weight/tibia length 0.053 ± 0.001 for Ob-ZSF1-CTRL vs 0.046 ± 0.002 for Ob-ZSF1-SAR247799 p<0.01, Le-ZSF1-CTRL 0.035 ± 0.001) and myocardial perivascular collagen content (p<0.001), independently of any changes in microvascular density. In young animals, SAR247799 improved endothelial function as assessed by the very low frequency bands of systolic blood pressure variability (mean ± SEM 67.8 ± 3.41 for Ob-ZSF1-CTRL  55.8 ± 4.27 or Ob-ZSF1-SAR247799, p<0.05  and 57.3 ± 1.82 Le-ZSF1-CTRL), independently of any modification of arterial blood pressure. In old animals, SAR247799 reduced urinary protein/creatinine ratio, an index of glomerular injury, (10.3 ± 0.621 vs 8.17 ± 0.231 for Ob-ZSF1-CTRL vs Ob-ZSF1-SAR247799, respectively, p<0.05 and 0.294 ± 0.029 for Le-ZSF1-CTRL, mean ± SEM) and the fractional excretion of electrolytes. Circulating lymphocytes were not decreased by SAR247799, confirming lack of S1P 1 desensitization.   Conclusions: These experimental findings suggest that S1P 1 activation with SAR247799 could improve LVH, cardiac diastolic and renal function in HFpEF patients .

scholarly journals Predominant Causes of Metabolic Syndrome in Adolescents vs Adults of Northwest India

2015 ◽  
Vol 49 (3) ◽  
pp. 121-125
Author(s):  
Anil Bhansali ◽  
Abhimanyu Saini ◽  
Daisy Sahni
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
The Metabolic Syndrome ◽  
Common Risk Factors ◽  
Northwest India

ABSTRACT Prevalence and distribution of metabolic syndrome was studied among 167 adolescents (aged 12—17 years) and 361 adults (aged 18—80 years) of Chandigarh zone of northwest India. Measurements of anthropometric variables, blood pressure, triglycerides (TGs), high-density lipoproteins and fasting blood glucose were taken. The metabolic syndrome was examined using criteria reported by national cholesterol education program adult treatment panel III. The overall prevalence of metabolic syndrome was 9% in adolescents and 40.7% in adults. No gender differences in its incidence were noted in adolescents or adults. In adolescents, the contribution of TGs was highest, high blood pressure and low high-density lipoprotein were of about equal significance as risk factors. The least common risk factors were fasting blood sugar and waist circumference. In adults, abdominal obesity was the most common inconsistent factor among the subjects having metabolic syndrome. Efforts should be made to screen out the metabolic syndrome positive subjects, as it is one of leading risk factors of cardiovascular disease and diabetes mellitus. How to cite this article Saini A, Sahni D, Bhansali A. Predominant Causes of Metabolic Syndrome in Adolescents vs Adults of Northwest India. J Postgrad Med Edu Res 2015;49(3):121-125.

scholarly journals Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects

2017 ◽  
Vol 10 (3) ◽  
pp. 86-92
Author(s):  
Vladimír Knezl ◽  
Ružena Sotníková ◽  
Zuzana Brnoliaková ◽  
Tatiana Stankovičová ◽  
Viktor Bauer ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Isolated Heart ◽  
Cardiovascular Effects ◽  
High Cholesterol ◽  
High Fat ◽  
Conscious Animals ◽  
Endothelium Dependent Relaxation

AbstractMetabolic syndrome belongs to the most important risk factors of cardiovascular diseases. The aim of this study was to investigate changes in cardiovascular system induced by high cholesterol and high fat diet (HCHF) in HTG rats and their influence by a pyridoindole antioxidant – SMe1EC2 (S). The effects of S were compared with those of atorvastatin (A). Male HTG rats were fed HCHF (1% cholesterol + 7.5% lard) for 4 weeks. S and A were administered p.o., 50 mg/kg b.w. Following experimental groups were used: Wistar rats (W), hypertriglyceridemic rats (HTG), HTG rats fed HCHF (CHOL), HTG+S (S-HTG), CHOL+S (S-CHOL), and CHOL+A (A-CHOL). Values of blood pressure (BP) and selected ECG parameters were monitored in conscious animals, functions of the isolated heart and aorta were analyzedex vivo. At the end of the experiment, systolic (sBP) and diastolic (dBP) blood pressure was increased in HTG and CHOL. S and A decreased BP in all treated groups. Accordingly with BP changes, the aortic endothelial function of CHOL was damaged. Both S and A administration ameliorated the endothelium-dependent relaxation to values of W. PQ and QTc intervals were prolonged in CHOL, while the treatment with S or A improved ECG findings. Prodysrhythmogenic threshold was decreased significantly in CHOL and both treatments returned it to the control values. In conclusion, HCHF increased BP, impaired endothelial relaxation of the aorta and potentiated susceptibility of myocardium to dysrhythmias. The effect of S on the changes induced by HCHF diet was more pronounced than that of A.

scholarly journals A G-protein-biased S1P1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0257929
Author(s):  
Maria Francesca Evaristi ◽  
Bruno Poirier ◽  
Xavier Chénedé ◽  
Anne-Marie Lefebvre ◽  
Alain Roccon ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Cardiac Hypertrophy ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
G Protein ◽  
Rat Model ◽  
Left Ventricular ◽  
Heart Weight ◽  
Functional Components

Aim Heart failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide with no approved treatment. Left ventricular hypertrophy (LVH) and diastolic dysfunction represent the structural and functional components of HFpEF, respectively. Endothelial dysfunction is prevalent in HFpEF and predicts cardiovascular events. We investigated if SAR247799, a G-protein-biased sphingosine-1-phosphate receptor 1 (S1P1) agonist with endothelial-protective properties, could improve cardiac and renal functions in a rat model of metabolic syndrome LVH and diastolic function. Methods 31- and 65-week-old obese ZSF1 (Ob-ZSF1) rats, representing adult and aged animals with LVH and diastolic dysfunction, were randomized to a chow diet containing 0.025% (w/w) of SAR247799, or control (CTRL) chow for 4 weeks. Age-matched lean ZSF1 (Le-ZSF1) rats were fed control chow. Echocardiography, telemetry, biochemical and histological analysis were performed to evaluate the effect of SAR247799. Results Echocardiography revealed that Ob-ZSF1 rats, in contrast to Le-ZSF1 rats, developed progressive diastolic dysfunction and cardiac hypertrophy with age. SAR247799 blunted the progression of diastolic dysfunction in adult and aged animals: in adult animals E/e’ was evaluated at 21.8 ± 1.4 for Ob-ZSF1-CTRL, 19.5 ± 1.2 for Ob-ZSF1-SAR247799 p<0.01, and 19.5 ± 2.3 for Le-ZSF1-CTRL (median ± IQR). In aged animals E/e’ was evaluated at 23.15 ± 4.45 for Ob-ZSF1-CTRL, 19.5 ± 5 for Ob-ZSF1-SAR247799 p<0.01, and 16.69 ± 1.7 for Le-ZSF1-CTRL, p<0.01 (median ± IQR). In aged animals, SAR247799 reduced cardiac hypertrophy (g/mm mean ± SEM of heart weight/tibia length 0.053 ± 0.001 for Ob-ZSF1-CTRL vs 0.046 ± 0.002 for Ob-ZSF1-SAR247799 p<0.01, Le-ZSF1-CTRL 0.035 ± 0.001) and myocardial perivascular collagen content (p<0.001), independently of any changes in microvascular density. In adult animals, SAR247799 improved endothelial function as assessed by the very low frequency bands of systolic blood pressure variability (mean ± SEM 67.8 ± 3.41 for Ob-ZSF1-CTRL 55.8 ± 4.27 or Ob-ZSF1-SAR247799, p<0.05 and 57.3 ± 1.82 Le-ZSF1-CTRL), independently of any modification of arterial blood pressure. In aged animals, SAR247799 reduced urinary protein/creatinine ratio, an index of glomerular injury, (10.3 ± 0.621 vs 8.17 ± 0.231 for Ob-ZSF1-CTRL vs Ob-ZSF1-SAR247799, respectively, p<0.05 and 0.294 ± 0.029 for Le-ZSF1-CTRL, mean ± SEM) and the fractional excretion of electrolytes. Circulating lymphocytes were not decreased by SAR247799, confirming lack of S1P1 desensitization. Conclusions These experimental findings suggest that S1P1 activation with SAR247799 may be considered as a new therapeutic approach for LVH and diastolic dysfunction, major components of HFpEF.

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