Browsing by Author "Vikas Agarwal"

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Aerobic glycolysis fuels platelet activation: Small-molecule modulators of platelet metabolism as anti-thrombotic agents
(Ferrata Storti Foundation, 2019) Paresh P. Kulkarni; Arundhati Tiwari; Nitesh Singh; Deepa Gautam; Vijay K. Sonkar; Vikas Agarwal; Debabrata Dash
Platelets are critical to arterial thrombosis, which underlies myocardial infarction and stroke. Activated platelets, regardless of the nature of their stimulus, initiate energy-intensive processes that sustain thrombus, while adapting to potential adversities of hypoxia and nutrient deprivation within the densely packed thrombotic milieu. We report here that stimulated platelets switch their energy metabolism to aerobic glycolysis by modulating enzymes at key checkpoints in glucose metabolism. We found that aerobic glycolysis, in turn, accelerates flux through the pentose phosphate pathway and supports platelet activation. Hence, reversing metabolic adaptations of platelets could be an effective alternative to conventional anti-platelet approaches, which are crippled by remarkable redundancy in platelet agonists and ensuing signaling pathways. In support of this hypothesis, small-molecule modulators of pyruvate dehydrogenase, pyruvate kinase M2 and glucose-6-phosphate dehydrogenase, all of which impede aerobic glycolysis and/or the pentose phosphate pathway, restrained the agonist-induced platelet responses ex vivo. These drugs, which include the anti-neoplastic candidate, di ch loroacetate, and th e Food and Drug Administration-approved dehydroepiandrosterone, profoundly impaired thrombosis in mice, thereby exhibiting potential as anti-thrombotic agents. © 2019 Ferrata Storti Foundation.
Fibroblast Growth Factor 23 Level and Cardiovascular Parameters in Children with Chronic Kidney Disease
(Springer, 2022) Gaurav Singh; Om P. Mishra; Abhishek Abhinay; Vikas Agarwal; Surendra P. Mishra; Amitnandan D. Dwivedi; Ankur Singh; Rajniti Prasad; Rabindra N. Mishra
Objective: To find out the serum fibroblast growth factor 23 (FGF-23) levels in different grades of CKD, and the prevalence of abnormal left ventricular mass index (LVMI), carotid intima–medial thickness (cIMT), and central pulse wave velocity (cPWV) and the risk factors including FGF-23 for these abnormalities. Methods: Fifty-nine patients of CKD with G2 to G5, aged 2–18 y were included. The LVMI, cIMT, and cPWV were measured using standard techniques, and serum intact FGF-23 levels were estimated at enrollment. Results: Median FGF-23 levels were significantly raised in all the grades of CKD than controls (p < 0.001), and also in G4 and G5 in comparison to G2&3 and in G5D than G5. Increased LVMI in 42 (71.2%), elevated cIMT in 30 (57.7%), and cPWV in 14 (26.9%) patients were found. The FGF-23 showed significant negative correlation with eGFRcr and positive with serum iPTH, phosphate and alkaline phosphatase levels, but had no correlations with LVMI, cIMT SDS, and cPWV SDS. Only systolic BP SDS (odds ratio 1.5, 95% CI 1.008–2.231, p = 0.046) was observed as a significant predictor for increased cIMT, while no variables had any association with abnormal LVMI and cPWV. Conclusions: Serum FGF-23 showed higher levels with increasing grades of CKD, but no significant association with cardiovascular parameters. Systolic BP SDS was found as a significant risk factor for increased cIMT in children with CKD. © 2021, Dr. K C Chaudhuri Foundation.
Nanogold-coated stent facilitated non-invasive photothermal ablation of stent thrombosis and restoration of blood flow
(Royal Society of Chemistry, 2024) Nitesh Singh; Paresh P. Kulkarni; Prashant Tripathi; Vikas Agarwal; Debabrata Dash
In-stent restenosis (ISR) and stent thrombosis (ST) are the most serious complications of coronary angioplasty and stenting. Although the evolution of drug-eluting stents (DES) has significantly restricted the incidence of ISR, they are associated with an enhanced risk of ST. In the present study, we explore the photothermal ablation of a thrombus using a nano-enhanced thermogenic stent (NETS) as a modality for revascularization following ST. The photothermal activity of NETS, fabricated by coating bare metal stents with gold nanorods generating a thin plasmonic film of gold, was found to be effective in rarefying clots formed within the stent lumen in various in vitro assays including those under conditions mimicking blood flow. NETS implanted in the rat common carotid artery generated heat following exposure to a NIR-laser that led to effective restoration of blood flow within the occluded vessel in a model of ferric chloride-induced thrombosis. Our results present a proof-of-concept for a novel photothermal ablation approach by employing coated stents in the non-invasive management of ST. © 2024 RSC.