Lipotoxicity: a driver of heart failure with preserved ejection fraction?

Figures

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  Figure 1. The three phenogroups of heart failure with preserved ejection fraction Data obtained from Cohen, J. et al., 2020 [31]. BNP, B-type natriuretic peptide; MMP9, matrix metalloproteinase 9; CKD, chronic kidney disease; TIMP-4, tissue inhibitor of metalloproteinase 4; HF, heart failure; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis.

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  Figure 2. Simple schematic of fatty acid metabolism in the cardiomyocyte under physiological conditions ADP, adenosine diphosphate; ATP, adenosine triphosphate; CD36, cluster of differentiation 36; CPT, carnitine palmitoyltransferase; ETC, electron transport chain; FA, fatty acid; FADH2, reduced flavin adenine dinucleotide; FAO, fatty acid oxidation; FATP1, fatty acid transport protein 1; GLUT4, glucose transporter type 4; NADH, reduced nicotinamide adenine dinucleotide; TAG, triacylglyceride; TCA cycle, tricarboxylic acid cycle.

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  Figure 3. Mechanisms by which lipid intermediates can promote the generation of reactive oxygen species (ROS), and by which ROS may go on to elicit diastolic dysfunction Physiological lipid handling is detailed in Figure 2 for comparison. PKC, protein kinase C; DAGs, diacylglycerols; Ca2+, calcium; PKG, protein kinase G; Nox2, nicotinamide adenine dinucleotide phosphate oxidase 2; NF-kB, nuclear factor kappa-light chain enhancer of activated B cells; MAPK, mitogen activated protein kinase; TGFb, transforming growth factor beta; O2−, superoxide anion radical.

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  Figure 4. Mechanisms by which lipid intermediates may induce mitochondrial dysfunction, and by which mitochondrial dysfunction may mediate diastolic dysfunction Physiological lipid handling is detailed in Figure 2 for comparison. ATP, adenosine triphosphate; ROS, reactive oxygen species; SERCA, sarco/endoplasmic reticulum calcium ATPase; Ca2+, calcium; O2−, superoxide anion radical.