The Peroxisome Proliferator-Activated Receptor <i>γ</i> Agonist Pioglitazone Protects Vascular Endothelial Function in Hypercholesterolemic Rats by Inhibiting Myeloperoxidase

Zhang, Dapeng; Wang, Yehong; Yi, Ming; Zhang, Suli; Wu, Ye

doi:10.1155/2020/1845969

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…Vascular relaxation induced by acetylcholine is dependent on the presence of endothelial cells and vascular relaxation induced by sodium nitroprusside is endothelium-independent [ 25 ]. Zhang et al showed that endothelium-dependent relaxation to acetylcholine is impaired by hypercholesterolemia but not endothelium-independent relaxation to sodium nitroprusside [ 26 ]. Our study indicated the consistent results.…”

Section: Discussionmentioning

confidence: 99%

Regular transient limb ischemia improves endothelial function and inhibits endothelial cell apoptosis to prevent atherosclerosis in rabbit

Zhang,

Wen,

et al. 2024

BMC Cardiovasc Disord

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Aims Regular transient limb ischemia (RTLI) can prevent atherosclerosis (AS) progression in hypercholesterolemic rabbits. This study aimed to investigate the minimum effective intensity and possible mechanisms of RTLI for preventing atherosclerosis. Methods Eighty rabbits were divided into eight groups: normal (N), high cholesterol (H), three RTLI [three RTLI cycles every other day (R3qod), three RTLI cycles daily (R3qd), and six RTLI cycles daily (R6qd), each cycle of RTLI included 5 min of limb ischemia followed by 5 min limb reperfusion], and three correlated sham RTLI [sham ischemia for 30 min once every other day (S3qod), sham ischemia for 30 min once daily (S3qd), and sham ischemia for 60 min once daily (S6qd)]. Rabbits in group N were kept normally, while the others were fed 1% cholesterol diet for 12 weeks. The RTLI and sham RTLI groups were received RTLI or sham RTLI procedure, respectively. The plaque area in the thoracic aorta was determined by oil red O staining, and quantifying the ratio of plaque area to intimal area (PA/IA). Endothelium-dependent and -independent relaxation were also determined. Endothelial cell were isolated from abdominal aorta of rabbits, and the apoptosis ratio was detected using flow cytometry. Results The PA/IA and early apoptotic cell ratio was significantly lower as well as the endothelium-dependent relaxation response was higher in group R6qd than those in groups H and S6qd, while those in the R3qod group was not significantly different from those in groups H and S3qod, as well as those in the R3qd group showed no significant difference compared to those in groups H and S3qd. Conclusions Six cycles of RTLI daily was the optimal effective intensity to prevent AS progression in rabbits. Endothelial function improvement and apoptosis inhibition might contribute to the anti-AS effects.

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Section: Discussionmentioning

confidence: 99%

Regular transient limb ischemia improves endothelial function and inhibits endothelial cell apoptosis to prevent atherosclerosis in rabbit

Zhang,

Wen,

et al. 2024

BMC Cardiovasc Disord

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“…Endothelial dysfunction is the first step in the development of atheroma. Hypercholesterolemia is one of the most common causes of endothelial dysfunction that causes stenosis of the aorta of the heart (Zhang et al, 2020). Cholesterol is required for some physiological activities.…”

Section: Introductionmentioning

confidence: 99%

Detection of the Atherosclerotic PCSK9 gene Inhibitors Through in silico Method to Improve Targeted Therapy

Sethuramalingam¹,

Ravi²,

Rajiah³

2022

BIOMEDNATPROCH

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The PCSK9 is one of the most important marks for the evolution of therapeutic agents for atherosclerosis because its interaction with low-density lipoprotein receptors causes atherosclerosis. Protein-ligand interactions help us to understand the true mechanism of pharmacological action. This study seeks to identify the most powerful suppression options for PCSK9. Initially, the reported ACE inhibitors were included in pharmacophore modeling using PharmaGist. Next, ZINCPHARMER was used to screen the selected model against a ZINC database to identify putative drug candidates docked to the target protein to understand the interactions. The 10 best pharmacological candidates for PCSK9 with a binding energy of 9.8-8.2 kcal mol-1 were identified by molecular docking and their pharmacokinetic properties and oral bioavailability were evaluated. The (S) severalplant obtained chemicals have been discovered, including anti-hypersensitive drugs such as “Canadine, Hesperetin, and Labetalol”. According to Biochemistry, these compounds formed a stable “protein-ligand” complex. The (S) canadine PCSK9 complex had the lowest RMSD and was the most stable. Future in vitro studies could identify (S) canadin as a promising atherosclerosis inhibitor for the evolution of novel PCSK9 inhibitors.

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“…Endothelial dysfunction is the first stage that leads to atherogenesis. Hypercholesterolemia is known as one of the most frequent causes of endothelial dysfunction, inducing constriction of large blood vessels in the heart [ 4 ]. Cholesterol itself is needed for many physiological processes.…”

Section: Introductionmentioning

confidence: 99%

Finding inhibitors for PCSK9 using computational methods

et al. 2021

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the key targets for atherosclerosis drug development as its binding with low-density lipoprotein receptor leads to atherosclerosis. The protein-ligand interaction helps to understand the actual mechanism for the pharmacological action. This research aims to discover the best inhibitory candidates targeting PCSK9. To start with, reported ACE inhibitors were incorporated into pharmacophore designing using PharmaGist to produce pharmacophore models. Selected models were later screened against the ZINC database using ZINCPHARMER to define potential drug candidates that were docked with the target protein to understand their interactions. Molecular docking revealed the top 10 drug candidates against PCSK9, with binding energies ranging from -9.8 kcal·mol-1 to -8.2 kcal·mol-1, which were analyzed for their pharmacokinetic properties and oral bioavailability. Some compounds were identified as plant-derived compounds like (S)-canadine, hesperetin or labetalol (an antihypertensive drug). Molecular dynamics results showed that these substances formed stable protein-ligand complexes. (S)-canadine-PCSK9 complex was the most stable with the lowest RMSD. It was concluded that (S)-canadine may act as a potential inhibitor against atherosclerosis for the development of new PCSK9 inhibitory drugs in future in vitro research.

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The Peroxisome Proliferator-Activated Receptor γ Agonist Pioglitazone Protects Vascular Endothelial Function in Hypercholesterolemic Rats by Inhibiting Myeloperoxidase

Cited by 8 publications

References 21 publications

Regular transient limb ischemia improves endothelial function and inhibits endothelial cell apoptosis to prevent atherosclerosis in rabbit

Regular transient limb ischemia improves endothelial function and inhibits endothelial cell apoptosis to prevent atherosclerosis in rabbit

Detection of the Atherosclerotic PCSK9 gene Inhibitors Through in silico Method to Improve Targeted Therapy

Finding inhibitors for PCSK9 using computational methods

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