Metabolic basis of cardiac dysfunction in cancer patients

Abstract

Purpose of review: The relationship between metabolism and cardiovascular diseases is complex and bidirectional. Cardiac cells must adapt metabolic pathways to meet biosynthetic demands and energy requirements to maintain contractile function. During cancer, this homeostasis is challenged by the increased metabolic demands of proliferating cancer cells.

Recent findings: Tumors have a systemic metabolic impact that extends beyond the tumor microenvironment. Lipid metabolism is critical to cancer cell proliferation, metabolic adaptation, and increased cardiovascular risk. Metabolites serve as signals which provide insights for diagnosis and prognosis in cardio-oncology patients.

Summary: Metabolic processes demonstrate a complex relationship between cancer cell states and cardiovascular remodeling with potential for therapeutic interventions.

Figure 1.. Metabolic enzymes and pathways to sense metabolism can impact cell state.

The exogenous uptake of fatty acids (FA) from the blood or tumor microenvironment facilitates energy provision and acetyl-CoA production through β-oxidation. Citrate is generated from glucose or amino acids. It can be used to synthesize acetyl-CoA and malonyl-CoA, which are both precursors for cholesterol and de novo fatty acid synthesis. The intersection between ACL, ACC, and FASN provides precursors for complex lipid synthesis, including storage lipids (TAG) and structural phospholipids (e.g. PG, PS, PE, PC) as part of cellular membranes. Abbreviations: ACL, ATP-dependent citrate lyase; ACC, acetyl-CoA carboxylase; ELOVL, Elongation of very long-chain fatty acids proteins; FA, fatty acid; FASN, fatty acid synthase; IDH, Isocitrate dehydrogenase; MUFA, monounsaturated fatty acids; PA, phosphatic acid; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PS, phosphatidylserine; PUFA, polyunsaturated fatty acids; TAG, triacylglycerol; SCD, stearoyl-CoA desaturase.