Comparison of Outcomes After Transcatheter Versus Surgical Repeat Mitral Valve Replacement

Arafat, Amr A.; Zahra, Ashraf; Alhossan, Abdulaziz; Alghosoon, Haneen; AlOtaiby, Mohammad; Albabtain, Monirah A; Adam, Adam I; Algarni, Khaled D.

doi:10.21470/1678-9741-2021-0341

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…MMVD affects 2%–3% of the human global population with approximately 15% of those affected requiring surgical valve replacements 6 . These treatments are invasive, costly, carry a risk for elderly adults and may lead to more severe complications including thrombosis, post‐operative infections and heart attack 7 . Currently, there are no medications to prevent, slow progression or reverse valve pathology associated with MMVD.…”

Section: Introductionmentioning

confidence: 99%

“… 6 These treatments are invasive, costly, carry a risk for elderly adults and may lead to more severe complications including thrombosis, post‐operative infections and heart attack. 7 Currently, there are no medications to prevent, slow progression or reverse valve pathology associated with MMVD. An improved understanding of the pathogenesis of MMVD is necessary for the development of novel therapeutic strategies for MMVD both in humans and dogs.…”

Section: Introductionmentioning

confidence: 99%

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TGF‐β‐induced PI3K/AKT/mTOR pathway controls myofibroblast differentiation and secretory phenotype of valvular interstitial cells through the modulation of cellular senescence in a naturally occurring in vitro canine model of myxomatous mitral valve disease

et al. 2023

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PI3K/AKT/mTOR signalling contributes to several cardiovascular disorders. The aim of this study was to examine the PI3K/AKT/mTOR pathway in myxomatous mitral valve disease (MMVD). Double-immunofluorescence examined expression of PI3K and TGF-β1 in canine valves. Valve interstitial cells (VICs) from healthy or MMVD dogs were isolated and characterized. Healthy quiescent VICs (qVICs) were treated with TGF-β1 and SC-79 to induce activated myofibroblast phenotypes (aVICs). Diseased valve-derived aVICs were treated with PI3K antagonists and expression of RPS6KB1 (encoding p70 S6K) was modulated using siRNA and gene overexpression. SA-β-gal and TUNEL staining were used to identify cell senescence and apoptosis, and qPCR and ELISA to examine for senescence-associated secretory phenotype. Protein immunoblotting was used to examine expression of phosphorylated and total proteins. TGF-β1 and PI3K are highly expressed in mitral valve tissues. Activation of PI3K/AKT/mTOR and increased expression of TGF-β are found in aVICs. TGF-β transitions qVICs to aVICs by upregulation of PI3K/AKT/mTOR. Antagonism of PI3K/ AKT/mTOR reverses aVIC myofibroblast transition by inhibiting senescence and promoting autophagy. Upregulation of mTOR/S6K induces transformation of senescent aVICs, with reduced capacity for apoptosis and autophagy. Selective knockdown of p70 S6K reverses cell transition by attenuating cell senescence, inhibiting apoptosis and improving autophagy. TGF-β-induced PI3K/AKT/mTOR signalling contributes to MMVD pathogenesis and plays crucial roles in the regulation of myofibroblast differentiation, apoptosis, autophagy and senescence in MMVD.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%