Subject(s)
Bioprosthesis , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Brachiocephalic Veins/surgery , Pericardium/transplantation , Sternum/surgery , Anastomosis, Surgical , Brachiocephalic Veins/injuries , Female , Humans , Middle Aged , Transplantation, Autologous , Treatment OutcomeABSTRACT
The fgf-2 gene encodes low molecular weight (LMW, 18 kDa) and high molecular weight (HMW, 22-24 kDa) forms that originate from alternative translation of a single mRNA and exhibit diverse biological functions. HMW fibroblast growth factor-2 (FGF-2) inhibits cell migration and induces cell transformation or growth arrest in a cell type- and dose-dependent fashion. Conversely, LMW FGF-2 upregulates both cell proliferation and migration in most cell types. Although transcriptional and translational regulation of HMW and LMW FGF-2 has been extensively investigated, little is known about post-translational control of their relative expression. Here we report that thrombin, a key coagulation factor and inflammatory mediator, cleaves HMW FGF-2 into an LMW FGF-2-like form that stimulates endothelial cell migration and proliferation. The effect of thrombin on these cell functions requires HMW FGF-2 cleavage. This post-translational control mechanism adds a novel level of complexity to the regulation of FGF-2, and links the activities of thrombin and FGF-2 in patho-physiological processes in which both molecules are expressed.
Subject(s)
Cell Movement/physiology , Cell Proliferation , Endothelial Cells/metabolism , Fibroblast Growth Factor 2/metabolism , Inflammation Mediators/metabolism , Protein Processing, Post-Translational/physiology , Thrombin/metabolism , Animals , Cell Movement/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Fibroblast Growth Factor 2/pharmacology , Humans , Inflammation Mediators/pharmacology , Mice , Molecular Weight , Thrombin/pharmacology , Transcription, Genetic/physiologyABSTRACT
Mitral valve prolapse (MVP) is a very common clinical condition that refers to a systolic billowing of one or both mitral valve leaflets into the left atrium. Improvements of echocardiographic techniques and new insights in mitral valve anatomy and physiology have rendered the diagnosis of this condition more accurate and reliable. MVP can be sporadic or familial, demonstrating autosomal dominant and X-linked inheritance. Three different loci on chromosomes 16, 11 and 13 have been found to be linked to MVP, but no specific gene has been described. Another locus on chromosome X was found to cosegregate with a rare form of MVP called 'X-linked myxomatous valvular dystrophy'. MVP is more frequent in patients with connective tissue disorders including Marfan syndrome, Ehlers-Danlos and osteogenesis imperfecta. The purpose of this review is to describe previous studies on the genetics and prevalence of MVP. The report warrants the need for further genetically based studies on this common, albeit not fully understood, clinical entity.
