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Researchers Identify ALPK2 as a Potential Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)
A groundbreaking study by researchers from Nagoya University Graduate School of Medicine has identified alpha-kinase 2 (ALPK2), an enzyme uniquely expressed in the heart, as a promising therapeutic target for heart failure with preserved ejection fraction (HFpEF). Published in The FASEB Journal, the research opens up new possibilities for treating this currently incurable and potentially fatal condition, which is on the rise worldwide.
HFpEF, which is characterized by the heart’s inability to relax properly during the filling phase, leads to insufficient blood flow and poor organ function. It is especially concerning because there are limited drug therapy options available for its management. ALPK2, which plays a key role in heart muscle fiber function, has been found to activate the TPM1 gene, a major regulator of heart contraction. This activation helps prevent the stiffening of the heart—a primary concern in HFpEF patients.
The research team, led by Tatsuya Yoshida, Mikito Takefuji, and Toyoaki Murohara from the Department of Cardiology, Nagoya University, discovered that ALPK2 plays an essential role in heart relaxation. They studied the gene expression of 518 protein kinases and found that ALPK2 was heart-specific. Further experiments using genetically modified mice revealed that low levels of ALPK2 caused heart dysfunction, while increased levels improved heart function by enhancing the phosphorylation of TPM1. This modification could provide a protective effect against HFpEF.
“This discovery represents a significant step forward in heart failure research,” said Yoshida. “ALPK2 overexpression suppressed the progression of diastolic dysfunction and improved heart failure-related symptoms, such as lung weight—a key indicator of heart failure severity.”
HFpEF is increasingly becoming a global health concern due to its limited treatment options. Currently, only two drugs—SGLT2 inhibitors and ARNI—are approved for its management. However, targeting ALPK2 may lead to the development of novel treatments that could significantly improve patient outcomes.
The research offers hope for patients suffering from this debilitating condition and paves the way for future therapeutic interventions that specifically target the ALPK2/TPM1 regulatory axis.
For more information on this study, refer to: Tatsuya Yoshida et al., ALPK2 Prevents Cardiac Diastolic Dysfunction in Heart Failure with Preserved Ejection Fraction, The FASEB Journal, 2024. DOI: 10.1096/fj.202402103R.
Disclaimer: This article is based on research findings and should not be considered as medical advice. Always consult a healthcare professional before making any decisions regarding treatment options for heart failure or any other medical condition.
