High FGF23 Levels Failed to Predict Cardiac Hypertrophy in Animal Models of Hyperphosphatemia and Chronic Renal Failure.

Increased fibroblast growth factor 23 (FGF23) levels are an independent predictor for adverse cardiac events suggesting a role as a link that drives cardiomyopathic changes in cardiorenal syndrome. The search for the underlying mechanism driving this interaction has led to the hypothesis that FGF23 causes pathogenic changes in the heart. Increased serum FGF23 has been independently shown to cause increased cardiac morbidity, mortality, and hypertrophy by signalling through FGF receptor 4.

The mechanism of osmotically induced sealing of cardiac t tubules.

Cardiac t tubules undergo significant remodeling in various pathological and experimental conditions, which can be associated with mechanical or osmotic stress. In particular, it has been shown that removal of hyposmotic stress can lead to sealing of t tubules. However, the mechanisms underlying the sealing process remain essentially unknown.

Cholesterol Protects Against Acute Stress-Induced T-Tubule Remodeling in Mouse Ventricular Myocytes.

Efficient excitation-contraction coupling in ventricular myocytes depends critically on the presence of the t-tubular network. It has been recently demonstrated that cholesterol, a major component of the lipid bilayer, plays an important role in long-term maintenance of the integrity of t-tubular system although mechanistic understanding of underlying processes is essentially lacking. Accordingly, in this study we investigated the contribution of membrane cholesterol to t-tubule remodeling in response to acute hyposmotic stress.

Small membrane permeable molecules protect against osmotically induced sealing of t-tubules in mouse ventricular myocytes.

Cardiac t-tubules are critical for efficient excitation-contraction coupling but become significantly remodeled during various stress conditions. However, the mechanisms by which t-tubule remodeling occur are poorly understood. Recently, we demonstrated that recovery of mouse ventricular myocytes after hyposmotic shock is associated with t-tubule sealing.

Sulindac confers high level ischemic protection to the heart through late preconditioning mechanisms.

We have recently shown that sulindac, an anti-inflammatory drug, enhances the killing of cancer cells, but not normal cells, under conditions of oxidative stress, by mechanisms unrelated to its cyclooxygenase (COX) inhibition. To further study the protective effect of sulindac on cells exposed to oxidative stress, we have investigated the effect of sulindac on rat cardiac myocytes subjected to hypoxia/reoxygenation, as well as in a Langendorff model of myocardial ischemia. Low levels of sulindac could protect cardiac myocytes against cell death due to hypoxia/reoxygenation.