Oncometabolic Tracks in the Heart.

The term cancer and the heart is readily associated with the cardiotoxicity of antineoplastic agents, such as anthracyclines or receptor tyrosine kinase inhibitors. This offers a different perspective, drawing attention to the consequences of metabolic dysregulation in cancers for energy substrate metabolism and contractile function of the heart and to common cellular strategies present in cancers and in the failing heart.

A PKM2 signature in the failing heart.

A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose.

Coronary microvascular pericytes are the cellular target of sunitinib malate-induced cardiotoxicity.

Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor used in the treatment of human malignancies. A substantial number of sunitinib-treated patients develop cardiac dysfunction, but the mechanism of sunitinib-induced cardiotoxicity is poorly understood. We show that mice treated with sunitinib develop cardiac and coronary microvascular dysfunction and exhibit an impaired cardiac response to stress.

Molecular mechanisms of hypertension and heart failure due to antiangiogenic cancer therapies.

Targeted antiangiogenic cancer therapies have revolutionized the treatment of highly vascularized cancers such as metastatic renal cell carcinoma and gastrointestinal stromal tumors. Such agents act by inhibiting the actions of proangiogenic growth factors and their receptor tyrosine kinases, which are known to be overexpressed in cancer. However, these factors also play an important role in normal cardiovascular physiology.

PKC-permitted elevation of sarcolemmal KATP concentration may explain female-specific resistance to myocardial infarction.

The female myocardium, relative to that of the male, exhibits sustained resistance to ischaemic tissue injury, a phenomenon termed sex-specific cardioprotection (SSC). SSC is dependent upon the sarcolemmal K(ATP) channel (sarcK(ATP)), and protein kinase C (PKC). Here we investigate whether PKC-mediated regulation of sarcK(ATP) concentration can explain this endogenous form of protection.

Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets.

Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality.

Low-intensity exercise training delays heart failure and improves survival in female hypertensive heart failure rats.

Exercise training improves functional capacity and quality of life in patients with heart failure. However, the long-term effects of exercise on mortality associated with hypertensive heart disease have not been well defined. In the present study, we investigated the effect of low-intensity exercise training on disease progression and survival in female spontaneously hypertensive heart failure rats.

Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure.

The mitochondrial phospholipid cardiolipin is required for optimal mitochondrial respiration. In this study, cardiolipin molecular species and cytochrome oxidase (COx) activity were studied in interfibrillar (IF) and subsarcolemmal (SSL) cardiac mitochondria from Spontaneously Hypertensive Heart Failure (SHHF) and Sprague-Dawley (SD) rats throughout their natural life span. Fisher Brown Norway (FBN) and young aortic-constricted SHHF rats were also studied to investigate cardiolipin alterations in aging versus pathology.