Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

Wihastuti, Titin Andri; Heriansyah, Teuku; Hanifa, Hanifa; Andarini, Sri; Sholichah, Zuhrotus; Sulfia, Yuni Hendrati; Adam, Aditya Angela; Refialdinata, Jeki; Lutfiana, Nurul Cholifah

doi:10.2478/enr-2018-0008

Cited by 10 publications

(6 citation statements)

References 21 publications

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“…The inhibition of Lp-PLA 2 with darapladib might be a valuable approach for patients in early stages of CAVS. Darapladib has proven to slow the development of atherosclerosis in animal models [67], but its anti-atherogenic effect has not been confirmed in randomized trials [68]. Although the pathophysiological processes of atherosclerosis are similar to CAVS, these findings cannot be directly transposed and proper investigations on CAVS patients are required to assess whether Lp-PLA 2 inhibition could be considered a novel therapeutic strategy for CAVS.…”

Section: Current Evidencementioning

confidence: 99%

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

Donato

Ferri

Lupo

et al. 2020

IJMS

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Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.

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Section: Current Evidencementioning

confidence: 99%

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

Donato

Ferri

Lupo

et al. 2020

IJMS

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“…The high prevalence of diabetes is expected to contribute to the increased prevalence of cardiovascular diseases related to atherosclerosis, including stroke, coronary artery disease, and peripheral vascular disease (Wihastuti et al. 2018 ). Atherosclerosis refers to the progressive thickening and hardening of the walls of medium and large arteries as a result of fat deposits on their inner lining.…”

Section: Introductionmentioning

confidence: 99%

Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation

Azemi

Mokhtar

Sharif

et al. 2021

Pharmaceutical Biology

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Context Atherosclerosis predisposes individuals to adverse cardiovascular events. Clinacanthus nutans L. (Acanthaceae) is a traditional remedy used for diabetes and inflammatory conditions. Objectives To investigate the anti-atherosclerotic activity of a C. nutans leaf methanol extract (CNME) in a type 2 diabetic (T2D) rat model induced by a high-fat diet (HFD) and low-dose streptozotocin. Materials and methods Sixty male Sprague-Dawley rats were divided into five groups: non-diabetic fed a standard diet (C), C + CNME (500 mg/kg, orally), diabetic fed an HFD (DM), DM + CNME (500 mg/kg), and DM + Metformin (DM + Met; 300 mg/kg). Treatment with oral CNME and metformin was administered for 4 weeks. Fasting blood glucose (FBG), serum lipid profile, atherogenic index (AI), aortic tissue superoxide dismutase levels (SOD), malondialdehyde (MDA), and tumour necrosis factor-alpha (TNF-α) were measured. The rats’ aortas were stained for histological analysis and intima-media thickness (IMT), a marker of subclinical atherosclerosis. Results The CNME-treated diabetic rats had reduced serum total cholesterol (43.74%; p = 0.0031), triglycerides (80.91%; p = 0.0003), low-density lipoprotein cholesterol (56.64%; p = 0.0008), AI (51.32%; p < 0.0001), MDA (60.74%; p = 0.0026), TNF-α (61.78%; p = 0.0002), and IMT (39.35%; p < 0.0001) compared to untreated diabetic rats. SOD level, however, increased (53.36%; p = 0.0326). These CNME effects were comparable to those in the metformin-treated diabetic rats. Conclusions C. nutans possesses anti-atherosclerotic properties, which may be due to reductions in vascular tissue oxidative stress, inflammation, and serum AI. Continued studies on atherosclerotic animal models are suggested.

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“…This evidence is shown in the Integrated Biomarker and Imaging Study 2 (IBIS-2) [61]. The mechanism of darapladib in halting the atherosclerotic progression has been verified in an animal study using the Sprague-Dawley rat model; this study signified that darapladib reduced the foam cells number, inducible nitric oxide synthase (i-NOS), and intracellular adhesion molecule-1 (ICAM-1) expression in the aorta at the early stages of atherosclerosis in type-2 diabetic model [62]. Consequently, there is a suggestion that altering the composition of atherosclerotic plaques to a less vulnerable state might decrease the risk of CVD outcomes.…”

Section: Evidence From Randomized Clinical Trialsmentioning

confidence: 79%

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

Santoso¹

2020

CCR

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Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is an enzyme family of phospholipase A 2 produced by the inflammatory cell in atherosclerotic plaque. It is transported in the circulation, attached mainly to low-density lipoprotein-cholesterol (LDL-C). It hydrolyzes glycerophospholipids particularly fatty acids at the sn-2 position and produces numerous bioactive lipids; and leads to endothelial dysfunction, atherosclerotic plaque inflammation, and development of the necrotic core in plaques.There are two kinds of phospholipase A 2 , namely: secretory phospholipase A 2 (sPLA 2 ) and Lp-PLA 2 . They are deemed as evolving predictors of cardiovascular disease (CVD) risk in hospitaland population-based studies, including healthy subjects, acute coronary syndromes (ACS) and patients with CVD. Unfortunately, Lp-PLA 2 inhibitor (darapladib) and s-PLA 2 inhibitor (varespladib methyl) failed to prove to lower the risk of composite CVD mortality, myocardial infarction and stroke in those with stable CVD and ACS.Herein, we describe the explanation based on the existing data why there is still a discrepancy among them. So, it highlights the opinion that phospholipase A 2 is merely the inflammatory biomarkers of CVD and playing an important role in atherosclerosis. Further, there is more spacious room to prove the causation.

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Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

Abstract: Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

Cited by 10 publications

References 21 publications

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation

Phospholipase A2 is an Inflammatory Predictor in Cardiovascular Diseases: Is there any Spacious Room to Prove the Causation?

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