Thrombospondins in the heart: potential functions in cardiac remodeling

Cardiac remodeling after myocardial injury involves inflammation, angiogenesis, left ventricular hypertrophy and matrix remodeling. Thrombospondins (TSPs) belong to the group of matricellular proteins, which are non-structural extracellular matrix proteins that modulate cell–matrix interactions and cell function in injured tissues or tumors. They interact with different matrix and membrane-bound proteins due to their diverse functional domains. That the expression of TSPs strongly increases during cardiac stress or injury indicates an important role for them during cardiac remodeling. Recently, the protective properties of TSP expression against heart failure have been acknowledged. The current review will focus on the biological role of TSPs in the ischemic and hypertensive heart, and will describe the functional consequences of TSP polymorphisms in cardiac disease

Anterior chamber depth and primary angle-closure glaucoma: an evolutionary perspective

Journal compilation © 2008 Royal Australian and New Zealand College of OphthalmologistsAnterior chamber depth is an inheritable trait which is affected by age, gender and race. Over 30 years ago, Alsbirk proposed that the shallow anterior chamber, which was typical of the Greenlandic Inuit, and which brings the iris in proximity to the cornea, may have evolved as a thermoregulatory adaptation to resist corneal freezing. Here, this hypothesis is revisited. Recent population genetic data which provide evidence for migration patterns of early humans are discussed and the notions of natural selection and ocular adaptation to cold climates are considered. Problems with the hypothesis are examined, but the idea that the shallow anterior chamber has a thermoregulatory role appears sound and suggests that shallow anterior chambers may have evolved in Homo sapiens living in north-east Asia during the last Ice Age.Robert J Casso

Dissociation of Cardiogenic and Postnatal Myocardial Activities of GATA4

Transcription factor GATA4 is a critical regulator of the embryonic and postnatal heart, but the mechanisms and cofactors required for its diverse functions are not fully understood. Here, we show that whereas the N-terminal domain of GATA4 is required for inducing cardiogenesis and for promoting postnatal cardiomyocyte survival, distinct residues and domains therein are necessary to mediate these effects. Cardiogenic activity of GATA4 requires a 24-amino-acid (aa) region (aa 129 to 152) which is needed for transcriptional synergy and physical interaction with BAF60c. The same region is not essential for induction of endoderm or blood cell markers by GATA4, suggesting that it acts as a cell-type-specific transcriptional activation domain. On the other hand, a serine residue at position 105, which is a known target for mitogen-activated protein kinase (MAPK) phosphorylation, is necessary for GATA4-dependent cardiac myocyte survival and hypertrophy but is entirely dispensable for GATA4-induced cardiogenesis. We find that S105 is differentially required for transcriptional synergy between GATA4 and serum response factor (SRF) but not other cardiac cofactors such as TBX5 and NKX2.5. The findings provide new insight into GATA4 mechanisms of action and suggest that distinct regulatory pathways regulate activities of GATA4 in embryonic development and postnatal hearts