Connective tissue growth factor (CTGF) is a member of the CCN family of six small secreted, cysteine-rich growth factors. The unique modular structure encompasses distinct functional domains which enable CTGF to interact with growth factors, surface receptors and matrix components. Widely expressed, CTGF has critical roles in embryonic development and the maintenance of normal cell and connective tissue function. It is also important for tissue repair following injury, and has been implicated in common diseases including atherosclerosis, pulmonary and renal fibrotic disorders and cancer. Factors that regulate CTGF transcription in response to exogenous stimuli, as well as downstream signalling pathways, have been described. However, only recently have studies begun to unravel how the functional domains within the CTGF modules orchestrate signals and control key biological processes. This article highlights how the structural and functional domains of CTGF and CTGF cleavage fragments integrate multiple extracellular events into cell signals.

severity differed between attributes, marginal rates of substitution between attributes should be compared with caution. The most important marginal rates of substitution were for physical energy.

1056α -Calcitonin gene-related peptide (αCGRP) is a potent vasodilator 1 and a hypotensive peptide. It is primarily localized to the sensory nervous system, with a perivascular innervation and considered to be the major cardiovascular form, as compared with the structurally similar βCGRP. CGRP acts via a G-protein-coupled receptor (calcitonin-like receptor) when dimerized with a single transmembrane-spanning receptor activity-modifying protein RAMP1 2 signaling via cAMP and other pathways. 3,4 CGRP does not play a primary role in the regulation of basal blood pressure (BP) in normal individuals 5,6 but is suggested to have protective properties, in cardiovascular disease, 7,8 including attenuation of vascular smooth muscle proliferation, 9 hyperplasia, 10,11 and stimulation of endothelial cell proliferation 12 and endothelial progenitor cells. 13 Evidence indicates the importance of CGRP in aggressive models of rodent hypertension that are centered on the kidney. 14,15 By comparison, there is little evidence of detailed analysis involving the ongoing influence of endogenous CGRP on hypertensive mechanisms and vascular remodeling, especially with regard to NO and oxidative stress pathways.Sensory nerve-derived CGRP release is stimulated by mechanisms that include angiotensin II (AngII) and sympathetic nerve reflexes, 3,4 baroreflex sensitivity, 16 and sensory nerve activators. 17,18 We have investigated the AngII hypertension model in wild-type (WT) and αCGRP knockout (αCGRPKO) mice that have similar resting BP. We hypothesized that αCGRP is protective against the onset and development of hypertension, and the aim was to identify mechanisms by which αCGRP is protective in this model. The novel findings show Abstract-α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels...