Cardiac natriuretic peptides: hormones with anticancer effects that localize to nucleus, cytoplasm, endothelium, and fibroblasts of human cancers

Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) synthesized by the same gene decrease within 24 hours up to 97% the number of human breast, colon, pancreatic, and prostate adenocarcinoma cells as well as human small-cell and squamous carcinomas of the lung cells. These peptide hormones completely inhibit the growth of human pancreatic adenocarcinomas growing in athymic mice. Immunocytochemical investigations have revealed that LANP, vessel dilator, kaliuretic peptide and ANP localize to the nucleus and cytoplasm of human pancreatic adenocarcinomas, which is consistent with their ability to decrease DNA synthesis in the nucleus of this cancer mediated by the intracellular messenger cyclic GMP. These peptide hormones also localize to the endothelium of capillaries and fibroblasts within these cancers. These are the first growth-inhibiting peptide hormones ever demonstrated to localize to the nucleus. Their ability to decrease the activation of growth promoting substances such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear Factor Kappa Beta (NFkB) suggests that in addition to inhibiting DNA synthesis their ability to decrease the activation of growth promoting substances helps to mediate their ability to inhibit the growth of human cancers

Heart valve function: a biomechanical perspective

Heart valves (HVs) are cardiac structures whose physiological function is to ensure directed blood flow through the heart over the cardiac cycle. While primarily passive structures that are driven by forces exerted by the surrounding blood and heart, this description does not adequately describe their elegant and complex biomechanical function. Moreover, they must replicate their cyclic function over an entire lifetime, with an estimated total functional demand of least 3×109 cycles. As in many physiological systems, one can approach HV biomechanics from a multi-length-scale approach, since mechanical stimuli occur and have biological impact at the organ, tissue and cellular scales. The present review focuses on the functional biomechanics of HVs. Specifically, we refer to the unique aspects of valvular function, and how the mechanical and mechanobiological behaviours of the constituent biological materials (e.g. extracellular matrix proteins and cells) achieve this remarkable feat. While we focus on the work from the authors' respective laboratories, the works of most investigators known to the authors have been included whenever appropriate. We conclude with a summary and underscore important future trends