Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction.

Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due to their clear cardiovascular benefits for heart failure with preserved ejection fraction (HFpEF) since there are no effective drugs that may improve clinical outcomes for these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin.

Corticosteroids significantly increase cystatin C levels in the plasma by promoting cystatin C production in rats.

Several studies have shown that non-renal factors such as corticosteroids may increase plasma cystatin C levels without affecting kidney function. However, the mechanisms underlying this are unclear. We hypothesized that corticosteroids may increase cystatin C levels in the plasma by promoting its production in tissues.

Dexamethasone-induced diuresis is associated with inhibition of the renin-angiotensin-aldosterone system in rats.

In heart failure (HF) patients, diuretics remain the cornerstone of therapy to relieve fluid retention. However, the resulting volume loss activates the renin-angiotensin-aldosterone system (RAAS), which blunts the decline in volume depletion and blood pressure. RAAS activation, in turn, compromises the diuretic decongesting effect.

Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA.

Corticosteroids Significantly Increase Serum Cystatin C Concentration without Affecting Renal Function in Symptomatic Heart Failure.

Background: Human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues. Its concentration in the circulation is mainly determined by glomerular filtration rate. However, non-renal factors, i.