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8 results on '"Yazdanyar, Mariam"'

2. The combination approach with Rhokinase inhibition and mechanical circulatory support in myocardial ischemia-reperfusion injury: Rho-kinase inhibition and ventricular unloading

Author

Miyahara, Shunsuke, primary, Jenke, Alexander, additional, Yazdanyar, Mariam, additional, Kistner, Julia, additional, Immohr, Moritz Benjamin, additional, Sugimura, Yukiharu, additional, Aubin, Hug, additional, Kamiya, Hiroyuki, additional, Okita, Yutaka, additional, Lichtenberg, Artur, additional, and Akhyari, Payam, additional

Published
2022
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4. AdipoRon Attenuates Inflammation and Impairment of Cardiac Function Associated With Cardiopulmonary Bypass–Induced Systemic Inflammatory Response Syndrome

Author

Jenke, Alexander, Yazdanyar, Mariam, Miyahara, Shunsuke, Chekhoeva, Agunda, Immohr, Moritz Benjamin, Kistner, Julia, Boeken, Udo, Lichtenberg, Artur, and Akhyari, Payam

Subjects
reactive oxygen species, Inflammation, Male, Cardiovascular Surgery, AdipoRon, Cardiopulmonary Bypass, Enzyme-Linked Immunosorbent Assay, Myocardial Reperfusion Injury, ischemia/reperfusion, Systemic Inflammatory Response Syndrome, Rats, Disease Models, Animal, Animal Models of Human Disease, Piperidines, Ischemia, Animals, Ventricular Function, Rats, Wistar, Oxidant Stress, Basic Science Research, Cells, Cultured, Original Research
Abstract

Background Cardiac surgery using cardiopulmonary bypass (CPB) frequently provokes a systemic inflammatory response syndrome, which is triggered by TLR4 (Toll‐like receptor 4) and TNF‐α (tumor necrosis factor α) signaling. Here, we investigated whether the adiponectin receptor 1 and 2 agonist AdipoRon modulates CPB‐induced inflammation and cardiac dysfunction. Methods and Results Rats underwent CPB with deep hypothermic circulatory arrest and were finally weaned from the heart‐lung machine. Compared with vehicle, AdipoRon application attenuated the CPB‐induced impairment of mean arterial pressure following deep hypothermic circulatory arrest. During the weaning and postweaning phases, heart rate and mean arterial pressure in all AdipoRon animals (7 of 7) remained stable, while cardiac rhythm was irretrievably lost in 2 of 7 of the vehicle‐treated animals. The AdipoRon‐mediated improvements of cardiocirculatory parameters were accompanied by increased plasma levels of IL (interleukin) 10 and diminished concentrations of lactate and K+. In myocardial tissue, AdipoRon activated AMP‐activated protein kinase (AMPK) while attenuating CPB‐induced degradation of nuclear factor κB inhibitor α (IκBα), upregulation of TNF‐α, IL‐1β, CCL2 (C‐C chemokine ligand 2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inducible nitric oxide synthase. Correspondingly, in cultured cardiac myocytes, cardiac fibroblasts, and vascular endothelial cells, AdipoRon activated AMPK, upregulated IL‐10, and attenuated activation of nuclear factor κB, as well as upregulation of TNF‐α, IL‐1β, CCL2, NADPH oxidase, and inducible nitric oxide synthase induced by lipopolysaccharide or TNF‐α. In addition, the treatment of cardiac myocytes with the AMPK activator 5‐aminoimidazole‐4‐carboxamide 1‐β‐D‐ribofuranoside resulted in a similar inhibition of lipopolysaccharide‐ and TNF‐α–induced inflammatory cell phenotypes as for AdipoRon. Conclusions Our observations indicate that AdipoRon attenuates CPB‐induced inflammation and impairment of cardiac function through AMPK‐mediated inhibition of proinflammatory TLR4 and TNF‐α signaling in cardiac cells and upregulation of immunosuppressive IL‐10.

Published
2021

8. Transforming growth factor-β1 promotes fibrosis but attenuates calcification of valvular tissue applied as a three-dimensional calcific aortic valve disease model.

Author

Jenke A, Kistner J, Saradar S, Chekhoeva A, Yazdanyar M, Bergmann AK, Rötepohl MV, Lichtenberg A, and Akhyari P

Subjects
Actins metabolism, Animals, Aortic Valve ultrastructure, Aortic Valve Stenosis pathology, Apoptosis, Calcinosis pathology, Calcium metabolism, Cells, Cultured, Cyclin D1 genetics, Cyclin D1 metabolism, Fibrosis, Sheep, Smad7 Protein metabolism, Wnt Signaling Pathway, beta Catenin metabolism, Aortic Valve metabolism, Aortic Valve pathology, Aortic Valve Stenosis metabolism, Calcinosis metabolism, Transforming Growth Factor beta metabolism
Abstract

Calcific aortic valve disease (CAVD) is characterized by valvular fibrosis and calcification and driven by differentiating valvular interstitial cells (VICs). Expression data from patient biopsies suggest that transforming growth factor (TGF)-β1 is implicated in CAVD pathogenesis. However, CAVD models using isolated VICs failed to deliver clear evidence on the role of TGF-β1. Thus, employing cultures of aortic valve leaflets, we investigated effects of TGF-β1 in a tissue-based three-dimensional (3-D) CAVD model. We found that TGF-β1 induced phosphorylation of Mothers against decapentaplegic homolog (SMAD) 3 and expression of SMAD7, indicating effective downstream signal transduction in valvular tissue. Thus, TGF-β1 increased VIC contents of rough endoplasmic reticulum, Golgi, and secretory vesicles as well as tissue levels of RNA and protein. In addition, TGF-β1 raised expression of proliferation marker cyclin D1, attenuated VIC apoptosis, and upregulated VIC density. Moreover, TGF-β1 intensified myofibroblastic VIC differentiation as evidenced by increased α-smooth muscle actin and collagen type I along with diminished vimentin expression. In contrast, TGF-β1 attenuated phosphorylation of SMAD1/5/8 and upregulation of β-catenin while inhibiting osteoblastic VIC differentiation as revealed by downregulation of osteocalcin expression, alkaline phosphatase activity, and extracellular matrix incorporation of hydroxyapatite. Collectively, these effects resulted in blocking of valvular tissue calcification and associated disintegration of collagen fibers. Instead, TGF-β1 induced development of fibrosis. Overall, in a tissue-based 3-D CAVD model, TGF-β1 intensifies expressional and proliferative activation along with myofibroblastic differentiation of VICs, thus triggering dominant fibrosis. Simultaneously, by inhibiting SMAD1/5/8 activation and canonical Wnt/β-catenin signaling, TGF-β1 attenuates osteoblastic VIC differentiation, thus blocking valvular tissue calcification. These findings question a general phase-independent CAVD-promoting role of TGF-β1. NEW & NOTEWORTHY Employing aortic valve leaflets as a tissue-based three-dimensional disease model, our study investigates the role of transforming growth factor (TGF)-β1 in calcific aortic valve disease pathogenesis. We find that, by activating Mothers against decapentaplegic homolog 3, TGF-β1 intensifies expressional and proliferative activation along with myofibroblastic differentiation of valvular interstitial cells, thus triggering dominant fibrosis. Simultaneously, by inhibiting activation of Mothers against decapentaplegic homolog 1/5/8 and canonical Wnt/β-catenin signaling, TGF-β1 attenuates apoptosis and osteoblastic differentiation of valvular interstitial cells, thus blocking valvular tissue calcification. These findings question a general phase-independent calcific aortic valve disease-promoting role of TGF-β1.

Published
2020
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