Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha

Westcott, C.; Genis, Amanda; Mthethwa, Mashudu; Graham, R. F.; Vuuren, Derick van; Huisamen, Barbara; Strijdom, Hans

doi:10.24170/14-1-1865

Cited by 2 publications

(3 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Atorvastatin has been shown to modulate thrombomodulin levels thereby conferring thromboresistance . Though no direct evidence of fenofibrate on the thrombus inhibition is available, several studies have demonstrated that fenofibrate improves endothelial function by regulating nitric oxide levels and therefore may contribute to thromboresistance indirectly . Thus, the atorvastatin–fenofibrate combination in the PLCL matrix was found to be beneficial in avoiding platelet adhesion, activation, and thrombus formation.…”

Section: Resultsmentioning

confidence: 99%

“…47 Though no direct evidence of fenofibrate on the thrombus inhibition is available, several studies have demonstrated that fenofibrate improves endothelial function by regulating nitric oxide levels and therefore may contribute to thromboresistance indirectly. 48 Thus, the atorvastatin− fenofibrate combination in the PLCL matrix was found to be beneficial in avoiding platelet adhesion, activation, and thrombus formation. Figure 9D shows the effect of the dual drug-loaded coating on the coagulation time of platelet poor plasma (PPP) using the APTT assay.…”

Section: In Vitro Degradationmentioning

confidence: 97%

See 1 more Smart Citation

Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating

Roopmani

Satheesh

Chellappan

et al. 2019

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

The pleiotropic effects of the atorvastatin–fenofibrate combination can be effectively harnessed for site-specific therapy to minimize stent-related complications. The present study aims to utilize the pleiotropic effects of these two drugs entrapped in a uniform and defect-free coating of poly(l-lactide-co-caprolactone) (PLCL) on a stainless steel stent to overcome stent-associated limitations. The stent coating parameters were optimized using ultrasonic spray coating technique to achieve a thin, smooth, and defect-free dual drug-loaded polymer coating on the stent. The dual drug-loaded polymer coated stent was characterized for surface morphology, thickness and coating integrity. In vitro drug release kinetics of the fabricated stent reveals a sustained release of both drugs for more than 60 days. Significant reduction of thrombus formation and adhesion of lipopolysaccharide-stimulated macrophages on the dual drug containing polymer-coated stent indicates that the drug combination possesses antithrombotic and anti-inflammatory effects. The combination did not adversely influence endothelialization but significantly retarded smooth muscle cell proliferation indicating its potential to overcome restenosis. No bacterial biofilm formation was observed on the stent due to the antibacterial activity of atorvastatin. A rat subcutaneous model was used to evaluate the biocompatibility of the coated stent and compared with the commercial stent. MicroCT, scanning electron microscopy, and morphometric analyses revealed that the coated stents exhibited excellent histocompatibility with no inflammatory response as evidenced from the cytokine levels measured 28 days postimplantation. Our data demonstrates for the first time that the combination of atorvastatin and fenofibrate can be successfully employed in cardiovascular stents to overcome the current limitations of conventional drug-eluting stents.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: In Vitro Degradationmentioning

confidence: 97%

Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating

Roopmani

Satheesh

Chellappan

et al. 2019

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

show abstract

“…The expression and activation by phosphorylation of several proteins involved in important myocardial signalling pathways were measured via Western blotting protocol routinely used in our laboratory [22,36,37]. To assess proteins under baseline conditions, the ventricles of the hearts from the fasted animals (allocated for the biochemical analyses) were freeze-clamped post-euthanasia and stored at -80°C.…”

Section: Methodsmentioning

confidence: 99%

Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats

et al. 2018

Self Cite

View full text Add to dashboard Cite

HIV-infection, certain antiretroviral drug classes, especially protease inhibitors (PI), and obesity are associated with increased ischaemic heart disease (IHD) risk. However, the effect of PI-free fixed dose combination (FDC) antiretroviral therapy (ART) on hearts exposed to ischaemia-reperfusion injury (I/R) is unknown, particularly in obesity. This is becoming relevant as World Health Organisation guidelines recommend a FDC ART containing (non-) nucleoside reverse transcriptase inhibitors (tenofovir (TDF), emtricitabine (FTC) and efavirenz (EFV)) as first-line HIV treatment. Additionally, obesity rates are rising in HIV-infected populations, not only in ART-experienced individuals, but also at the time of ART initiation, which may further increase the risk of IHD. Therefore, we investigated the effects of PI-free FDC ART in myocardial I/R-exposed hearts from obese rats. Obesity was induced in male wistar rats via a 16-week high calorie diet. At week 10, treatment with a FDC ART drug containing TDF/FTC/EFV was initiated. Biometric and metabolic parameters, as well as myocardial functional recovery and infract size (IS), and myocardial signalling proteins following I/R were assessed after 16 weeks. Obese rats presented with increased body and intraperitoneal fat mass, elevated triglyceride and TBARS levels, whilst the hearts responded to I/R with impaired functional performance and increased IS. The FDC ART treatment did not alter biometric and metabolic parameters in obese rats. In a novel finding, ART protected obese hearts against I/R as shown by improved functional performance and smaller IS vs. untreated obese hearts. Cardioprotection was underscored by increased myocardial phosphorylated endothelial nitric oxide synthase (eNOS) and reduced AMP-kinase levels. In conclusion, these results demonstrate for the first time, that 6-weeks treatment of obese rats with a FDC ART drug specifically containing TDF/FTC/EFV conferred cardioprotection against I/R. The FDC ART-induced cardioprotection was seemingly unrelated to metabolic changes, but rather due to direct cardiac mechanisms including the up-regulation of myocardial eNOS.

show abstract

Fenofibrate protects endothelial cells against the harmful effects of TNF-alpha

Cited by 2 publications

References 46 publications

Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating

Development of Dual Drug Eluting Cardiovascular Stent with Ultrathin Flexible Poly(l-lactide-co-caprolactone) Coating

Treatment with a fixed dose combination antiretroviral therapy drug containing tenofovir, emtricitabine and efavirenz is associated with cardioprotection in high calorie diet-induced obese rats

Contact Info

Product

Resources

About