Acute Kidney Injury Induces Remote Cardiac Damage and Dysfunction Through the Galectin-3 Pathway.

Acute kidney injury is associated with increased risk of heart failure and mortality. This study demonstrates that acute kidney injury induces remote cardiac dysfunction, damage, injury, and fibrosis via a galectin-3 (Gal-3) dependent pathway. Gal-3 originates from bone marrow-derived immune cells. Cardiac damage could be prevented by blocking this pathway.

A Role of Remote Organs Effect in Acute Kidney Injury Outcome.

Acute kidney injury (AKI) has been associated with both short- and long-term outcomes. To date, there is still a debate whether the increase risk of morbidity and mortality is directly due to AKI occurrence. There is, however, a potential causal impact of AKI on outcome, but evidence of this association is yet lacking. The hypothesis of remote organ damage and dysfunction (heart, lung, liver, brain, etc.) has emerged over the last decade and may explain the reason for the potential negative impact of AKI on outcome. The aim of this review was to describe findings concerning the remote effect of AKI in animal models and human studies.

Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve cardiac function and metabolism in diabetic animals in contrast to lean animals.

Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice.

Galectin-3 (Gal-3) is involved in inflammation, fibrogenesis, and cardiac remodeling. Previous evidence shows that Gal-3 interacts with aldosterone in promoting macrophage infiltration and vascular fibrosis and that Gal-3 genetic and pharmacological inhibition prevents remodeling in a pressure-overload animal model of heart failure. We aimed to explore the contribution of Gal-3 and aldosterone in mechanisms leading to heart failure in a murine model. Male mice with cardiac-specific hyperaldosteronism underwent isoproterenol subcutaneous injections, to be then randomized to receive placebo, a Gal-3 inhibitor (modified citrus pectin [MCP]), an aldosterone antagonist (potassium canrenoate), or MCP+canrenoate for 14 days. Isoproterenol induced a rapid and persistent decrease in left ventricular fractional shortening (-20% at day 14); this was markedly improved by treatment with either MCP or canrenoate (both P<0.001 versus placebo). MCP and canrenoate also reduced cardiac hypertrophy and fibrosis and the expression of genes involved in fibrogenesis (Coll-1 and Coll-3) and macrophage infiltration (CD-68 and MCP-1). After isoproterenol, Gal-3 gene expression (P<0.05 versus placebo) and protein levels (-61% and -69% versus placebo) were decreased by both canrenoate and MCP. The combined use of antagonists of Gal-3 and aldosterone resulted in more pronounced effects on cardiac hypertrophy, inflammation, and fibrosis, when compared with either MCP or canrenoate alone. Inhibition of Gal-3 and aldosterone can reverse isoproterenol-induced left ventricular dysfunction, by reducing myocardial inflammation and fibrogenesis. Gal-3 likely participates in mechanisms of aldosterone-mediated myocardial damage in a heart failure murine model with cardiac hyperaldosteronism. Gal-3 inhibition may represent a new promising therapeutic option in heart failure.