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      Vericiguat promotes preservation of mitophagy and mitochondrial function in human cardiac myocytes. In vitro study

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            Abstract

            Vericiguat, a soluble guanylate cyclase stimulator, provides additional benefits to standard treatment against heart failure (HF). It is known that decreased mitochondrial function and/or deficient process to selectively remove damaged mitochondria (mitophagy) in cardiac cells are crucial in HF progression. The aim was to study vericiguat effect on mitophagy and mitochondrial function in an in vitro study under pro-inflammatory conditions, simulating HF conditions. Human Cardiac Myocytes (HCM) were incubated in absence (Control-group) and presence of TNF-α (50 ng/ml) (TNF-group). 30 μΜ of Vericiguat was added after 24h TNF-α incubation (50 ng/ml) (TNF+Ver-group). Expression levels of proteins closely involved in mitophagy Pink-1 and Parkin, cGMP production and mitochondrial function (∆Ψm) were analyzed using Dot-blot and commercial kits. Results represent mean±SEM of six experiments/group. Results confirmed increased cGMP production induced by vericiguat. ∆Ψm was reduced in HCM incubated with TNF-α respect to control-group, vericiguat addition reverted the decreasing ∆Ψm induced by TNF-α (∆Ψm (Fluorescence units): control-group:2.30±0.11 vs TNF-group:0.98±0.02;p<0.001;TNF+Ver-group:1.28±0.04;p<0.001 respect to TNF-group). Expression of Pink-1 and Parkin were found significantly decreased in TNF-group compared to control-group, however, Pink-1 and Parkin expression in the TNF+Ver-group showed similar values to them found in the control group (Pink-1 expression (arbitrary densitometric units):control-group:322.52±3.41 vs TNF-group:92.21±1.67;p<0.040;TNF+Ver-group:289.50±3.07;p=0.001 respect to TNF-group; Parkin expression (arbitrary densitometric units):control-group:251.54±2.18 vs TNF-group:102.82±1.23;p=0.004;TNF+Ver-group:288.01±3.08;p=0.002 respect to TNF-group). Significant positive correlation was found between mitophagy related proteins expression and cGMP levels in HCM. As conclusion, vericiguat improved mitochondrial function in HCM under pro-inflammatory conditions, which may be explained by preservation of mitophagy in a cGMP level-dependent manner.

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            Author and article information

            Conference
            cGMP: Generators, Effectors and Therapeutic Implications Conference
            27 March 2024
            Affiliations
            [1 ] Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Madrid, Spain ( https://ror.org/014v12a39)
            [2 ] Medicine Department. School of Medicine, Complutense University, Madrid, Spain ( https://ror.org/02p0gd045)
            [3 ] Public Health and Maternal, Child Health Department, School of Medicine, Complutense University, Madrid, Spain ( https://ror.org/02p0gd045)
            Author notes
            Author information
            https://orcid.org/0000-0001-8412-9482
            https://orcid.org/0000-0001-5551-5181
            https://orcid.org/0000-0001-5906-9393
            https://orcid.org/0000-0003-0686-4208
            Article
            10.14293/CGMP.24000059.v1
            706f49a1-5102-404d-9ca9-b5da0f7e9484

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            cGMP: Generators, Effectors and Therapeutic Implications
            11
            Lübeck
            June 28-30, 2024
            History
            : 27 March 2024
            Funding
            Funded by: funder-id http://dx.doi.org/10.13039/100004326, Bayer;
            Award ID: 22010
            Categories

            The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
            Cardiovascular Medicine
            Human Cardiac Myocytes,Vericiguat,cGMP,mitochondrial function,mitophagy

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