Myeloid KLF2 and Atherosclerosis (p 1294)
KLF2 expression in myeloid cells reduces atherosclerosis aggression, report Lingrel et al.
The transcription factor Kruppel-like factor (KLF)2 is known for having an essential role in vascular development and integrity—a fact that has sparked investigations into whether it also participates in vascular disease pathologies. KLF2 deficiency has been shown to exacerbate atherosclerosis in adult mice with hypercholesterolemia, for example. The KLF2-deficient mice have reduced levels of the protein in all cells, whereas atherosclerosis mainly involves endothelial, smooth muscle, and immune cells. Because KLF2 is suppressed during inflammation and is required for immune cell quiescence, Lingrel et al decided to see whether specific depletion of KLF2 in immune cells—myeloid cells, to be precise—would also exacerbate atherosclerosis. It did. Atherosclerosis-prone mice whose myeloid cells lacked KLF2 had increased neutrophils and macrophages in their vascular lesions; the reason being that without KLF2, these cells were stickier—they adhered more robustly to endothelial cells than their wild-type counterparts. Interestingly, in addition to lowering cholesterol, statins have been reported also to boost KLF2 expression in various cell types. If myeloid cells are affected by statins this way, it could be adding to the drug's beneficial effect.
Islet-1 in the Adult Murine Heart (p 1303)
Contrary to previous suggestions, Islet-1 does not mark adult cardiac progenitors, say Weinberger et al.
Cells isolated from embryonic and newborn mouse hearts that express the transcription factor Islet-1 are able to give rise to different types of heart cells, suggesting that Islet-1 might be a marker of cardiac progenitor cells. It has been reported that Islet-1 cells are present in the adult heart. This has led to the hope that activating these cells might help repair myocardial injuries. Weinberger et al examined genetically engineered mice in which expression of the Islet-1 gene made cells turn blue. In the hearts of these mice, blue cells were restricted to 3 particular locations—the interatrial septum, the walls of the aorta and pulmonary artery, and between the right atrium and superior vena cava. This latter location is where the sinoatrial node (SAN) lies, and staining the hearts with a SAN marker confirmed that some SAN cells expressed Islet-1. SAN tissue from humans and wild-type mice was also found to express abundant Islet-1 mRNA. Furthermore, for the most part, the number and localization of blue cells was unaltered after myocardial infarction. Taken together, the results provide no evidence to support the view that Islet-1 marks progenitor cells in adult hearts but that it might be a good marker for SAN cells.
ACE2 and Diabetic Cardiomyopathy (p 1322)
Boosting levels of ACE2 enzyme could keep cardiovascular complications of diabetes under control, say Patel et al.
Cardiovascular complications are the major cause of death in people with diabetes, and the rising number of diabetics is leading to an epidemic of cardiovascular disease and heart failure. Among the key mechanisms considered to contribute to the diabetes-associated circulatory problems is the activation of the renin-angiotensin system (RAS), which can promote increases in blood pressure but can also promote pathological remodeling of the heart in diabetes. Patel et al found that cardiac angiotensin-converting enzyme 2 (ACE2) is upregulated in mouse models of diabetes. This enzyme negatively regulates the RAS, and, sure enough, when Patel et al deleted ACE2 in insulin-deficient, nonobese mice, their symptoms were exacerbated. The mice displayed increased angiotensin II levels, which led to adverse cardiac remodeling, systolic dysfunction, and vascular oxidative stress and impaired flow-mediated dilation. The authors conclude that the increase in ACE2 in the hearts of these mice is a crucial compensatory mechanism that is activated to protect the heart. They also suggest that boosting ACE2 expression or activity could minimize secondary cardiovascular complications, at least in states of insulin deficiency.
Written by Ruth Williams.
- © 2012 American Heart Association, Inc.