Role of Tryptase in Abdominal Aortic Aneurysm (p 1316)
Zhang et al reveal tryptase as a mast cell mediator of aortic aneurysm.
Abdominal aortic aneurysms (AAAs) that develop because of the expansion of the artery like a balloon can be life-threatening in the event of rupture. The hope is that AAAs can be caught early and surgically repaired. Zhang et al have now found that in patients with AAA, serum tryptase levels correlate with expansion and pose a risk for later surgical repair and mortality. This suggests that tryptase might serve as a useful biomarker for AAA development. The team also showed that high levels of serum tryptase were a result of an increase in mast cells, previously described in AAA patients and in mouse models of AAA. Furthermore, the increased tryptase was not just a reflection of AAA development, it was actually the cause. Mice lacking the gene for tryptase were protected from experimentally induced AAA lesion expansion, the team found. These mice had fewer inflammatory and apoptotic cells at AAA lesions and less elastin degradation. Importantly, methods used to block tryptase activity —such as protease inhibitors—might offer beneficial treatments for AAA patients, say the authors.
CCICR and RhoA/ROCK in Vascular Smooth Muscle (p 1348)
Fernandez-Tenorio et al discover the wide-ranging cellular effects of a calcium channel in sustained vascular smooth muscle contraction.
Sustained vascular smooth muscle contraction is associated with pathologies such as hypertension, angina, and cardiac arrhythmias. Although both L-type voltage-gated calcium channels (VGCCs) and contractile machinery sensitization by RhoA/Rho kinase have been implicated in sustained contraction, it is unclear how these elements are mechanistically interrelated. VGCCs both enable the influx of calcium from extracellular pools and control release of calcium from intracellular stores—namely, through the sarcoplasmic reticulum. The latter pathway is controlled via the activation of G protein/phospholipase C and other downstream cell signaling molecules. Fernandez-Tenorio et al showed that this so-called metabotropic pathway also activated the RhoA/Rho-mediated contractile machinery sensitization. These findings indicate that the effect of VGCCs on sustained vascular smooth muscle cell contraction encompasses more downstream pathways than previously thought. The results could be useful for optimizing treatments for hypertension, angina, and arrhythmias, say the team.
HOXC9 and Endothelial Quiescence (p 1367)
HOXC9 halts vertebrate vascular development, report Stoll et al.
Transcription factors of the homeobox (HOX) family are important developmental morphogenes involved in the growth of numerous bodily structures and systems. Their role in vascular development, however, is not well understood. HOXC9 is expressed in blood vessels, which prompted Stoll et al to investigate whether this family member has any role in vascular development. They found that HOXC9 displayed a distinctive pattern of expression in cultured human vascular endothelial cells: sparsely growing cells had little of the factor, but expression increased along with cell density. Apparently, HOXC9 inhibited cell proliferation and the ability of the cells to migrate and form tubes in culture. Further experiments revealed that HOXC9 suppressed the expression of the interleukin (IL)-8 gene—a known angiogenic factor. Indeed, HOXC9's effect on migration and tube formation could be reversed by administering exogenous IL-8. Proliferation remained unaltered, however, suggesting that HOXC9 targets another factor(s) to exert this effect. Using Zebrafish embryos, the team showed that the overexpression of HOXC9, or indeed loss of IL-8, inhibited normal in vivo vascular development. Given that IL-8 can promote angiogenesis in certain tumors, boosting HOXC9 may be a good therapeutic countermeasure.
Written by Ruth Williams
- © 2011 American Heart Association, Inc.