A brand new therapeutic goal for a deadly type of coronary heart failure: ALPK2. Credit score: 2024 Federation of American Societies for Experimental Biology (FASEB).
Researchers from the Nagoya College Graduate College of Drugs recognized an enzyme, alpha-kinase 2 (ALPK2) that’s particularly expressed within the coronary heart. They discovered that the enzyme could forestall a stiff coronary heart by activating the gene TPM1 in coronary heart muscle fibers. ALPK2 is a promising new therapeutic goal for the remedy of coronary heart failure, particularly coronary heart failure with preserved ejection operate (HFpEF). The work is printed in The FASEB Journal.
The variety of coronary heart failure sufferers is growing worldwide. Particularly, HFpEF is a rising world concern as it’s incurable, doubtlessly deadly, and there are restricted drug remedy choices. HFpEF sufferers are characterised by a coronary heart that fails to chill out correctly throughout the filling section, resulting in inadequate blood move to fulfill the physique’s wants.
The method of protein phosphorylation is central to regulating varied features within the physique, together with how effectively the guts pumps blood out. The method is managed by enzymes known as protein kinases, which add a phosphate group to particular amino acids on track proteins. This modification adjustments the protein’s construction, inflicting adjustments in its exercise and interactions with different molecules. Disruptions within the enzyme’s exercise play a key position in hearts changing into stiff.
The group investigated the gene expression of 518 protein kinase enzymes, revealing ALPK2 as a heart-specific kinase of curiosity. To grasp its position, they in contrast mice with out the gene that creates the enzyme with those who had exceptionally excessive ranges of the gene, resulting in an abundance of ALPK2.
The mice with low ranges confirmed elevated weaknesses within the aging-related potential of the guts to chill out and fill with blood. Alternatively, the mice with overexpression of ALPK2 had elevated phosphorylation of the amino acid tropomyosin 1 (TPM1), a significant regulator of coronary heart contraction. As HFpEF sufferers have decreased TPM1, elevated phosphorylation of TPM1 would possible have a protecting impact in opposition to the illness.
“ALPK2-overexpression suppressed progression of diastolic dysfunction. In addition, it improved lung weight, which is often used as an index of heart failure,” Tatsuya Yoshida summarized.
“HFpEF is a growing global concern due to limited drug therapy options. Currently, there are only two drugs for HFpEF: SGLT2 inhibitor and ARNI. The ALPK2/TPM1 regulatory axis may provide a unique therapeutic target for HFpEF, allowing the development of new treatment options that target ALPK2 in the future.”
The crew consists of Tatsuya Yoshida, Mikito Takefuji, and Toyoaki Murohara within the Division of Cardiology, Nagoya College Graduate College of Drugs.
Extra info:
Tatsuya Yoshida et al, ALPK2 prevents cardiac diastolic dysfunction in coronary heart failure with preserved ejection fraction, The FASEB Journal (2024). DOI: 10.1096/fj.202402103R
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Enzyme ALPK2: A therapeutic goal for a deadly type of coronary heart failure (2025, January 30)
retrieved 30 January 2025
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