Sex-Specific Effect of MTSS1 Downregulation on Dilated Cardiomyopathy.

MTSS1 (metastasis suppressor 1) is an I-BAR protein that regulates cytoskeleton dynamics through interactions with actin, Rac, and actin-associated proteins. In a prior study, we identified genetic variants in a cardiac-specific enhancer upstream of that reduce human left ventricular (LV) MTSS1 expression and associate with protection against dilated cardiomyopathy (DCM). We sought to probe these effects further using population genomics and murine models.

Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction.

Rationale: Nitrate-rich beetroot juice has been shown to improve exercise capacity in heart failure with preserved ejection fraction, but studies using pharmacological preparations of inorganic nitrate are lacking.

Objectives: To determine (1) the dose-response effect of potassium nitrate (KNO) on exercise capacity; (2) the population-specific pharmacokinetic and safety profile of KNO in heart failure with preserved ejection fraction.

Methods And Results: We randomized 12 subjects with heart failure with preserved ejection fraction to oral KNO (n=9) or potassium chloride (n=3).

Effect of Heart Failure With Preserved Ejection Fraction on Nitric Oxide Metabolites.

Endothelial function may be deranged in heart failure with preserved ejection fraction (HFpEF). Serum NO-derived metabolites (NO) might provide a biochemical surrogate of endothelial function in patients with heart failure (HF). We measured serum NO in 415 participants in the Penn HF Study.

The mitogen-activated protein kinase pathway tonically inhibits both basal and IGF-I-stimulated IGF-binding protein-5 production in mammary epithelial cells.

The IGF system plays a key role in mammary gland growth and development. Our lab previously reported that IGF-I primarily regulates IGF-binding protein (BP)-3 in bovine mammary epithelial cells (MEC) and IGFBP-5 in mammary fibroblasts (MF). Presently, we examined the signaling pathways used by IGF-I to elicit this distinct, cell-type specific regulation.