Abcg2 and Division of Cardiac Stem Cells (p 27)
Sereti et al identify cell-surface protein Abcg2 as a promoter of both proliferation and symmetric cell division in cardiac progenitors.
It is currently believed that to maintain homeostasis, cardiac progenitor cells divide asymmetrically, giving rise to one cell that differentiates and another that replaces the progenitor. After an injury, however, it is thought that the progenitor cell population is depleted as these cells differentiate into cardiac myocytes, and that replenishment of the progenitors occurs by symmetrical division. Understanding the molecular mechanisms that drive cardiac progenitor cell division might therefore be useful in developing potential cell-based therapies for heart repair. The cell surface protein Abcg2, which is expressed on cardiac progenitors, was previously found to regulate proliferation in these cells. Now Sereti et al have discovered that this protein not only promotes cell-cycle progression, but also symmetric division. Progenitor cells that lacked Abcg2 tended to arrest before DNA replication—at G0 and G1 stages of the cell cycles—while those that did divide tended to do so asymmetrically. Thus, the authors suggest that regulating Abcg2 levels after injury could maximize the regenerative potential of the heart.
S100A1 in Angiogenesis (p 66)
Lack of calcium-binding protein S100A1 in ischemic tissue prevents the production, and thus protective effects, of nitric oxide, say Most et al.
It is well known that nitric oxide (NO) protects blood vessels during ischemia. And it has also been reported that the calcium-binding protein S100A1, expressed in endothelial cells, increases NO synthesis via eNOS. Furthermore, S100A1 has been found to be crucial for endothelial function. Most et al now bring these separate pieces of evidence together and show that ischemic tissue samples taken from both patients with chronic critical limb ischemia and mice with induced limb ischemia display a near-complete loss of S100A1 expression, which is associated with a decrease in NO. The team created S100A1 knockout (SKO) mice and showed that these animals have impaired reperfusion and neovascularization after ischemia. However NO injections restored the angiogenic potential in these mice. The team also showed that S100A1 directly binds and activates eNOS and also indirectly activates the enzyme by suppressing the activity of an eNOS inhibitor. Altogether, these results show that S100A1 is a critical regulator of eNOS and that it could be a therapeutically important protein for the treatment of ischemic vascular disease.
Stem Cells in Dilated Cardiomyopathy (p 165)
Bone marrow stem cell transplants lead to long-term improvements in heart function for cardiomyopathy patients, report Vrtovec et al.
Vrtovec et al report the results of a 5-year follow-up study of dilated cardiomyopathy (DCM) showing that patients who received intracoronary bone marrow transplants have better exercise capacity, heart function and better chance of survival compared with patients that did not receive the treatment. The 55 randomly selected DCM patients who received the bone marrow generally had higher left ventricle ejection fraction, could walk further, had lower levels of NT-proBNP—a protein marker of heart failure—in their blood, and fewer of them died. Interestingly, symptomatic improvement correlated with the extent to which the bone marrow cells integrated into the myocardium—which was assessed by radioactive tracing on the day of the transplantation. The improvements generally tended to be most significant within the first few years of the procedure. Ejection fraction, for example, showed a dramatic difference between test subjects and controls after one year, which persisted for a further two years, but then started to decline. This suggests that repeating the treatment regimen every few years, might further improve outcomes in DCM patients, say the authors.
- © 2012 American Heart Association, Inc.