Cardiac TRPM7 Causes Diabetic Heart Failure With Preserved Ejection Fraction

Abstract

Hypomagnesemia (HypoMg) and subsequent oxidative stress cause diabetic cardiac diastolic dysfunction and heart failure with preserved ejection fraction. A Mg²⁺ transporter with channel and kinase function, transient receptor potential cation channel subfamily M 7 (TRPM7), is upregulated in HypoMg. Diabetes mellitus mice had HypoMg and elevated TRPM7 expression in the heart. TRPM7 kinase mediated mitochondrial dysfunction and cardiac diastolic dysfunction in HypoMg. TRPM7 kinase enhanced mitochondrial Fgr expression, with subsequent complex II dysfunction and mitochondrial reactive oxygen species overproduction. Inhibition of TRPM7 kinase represents a potential novel therapeutic strategy to treat diabetic heart failure with preserved ejection fraction.