Kruppel-Like Factors Established As Master Regulators of Vascular Health

Case Western Reserve researchers have identified a genetic factor that blocks the blood vessel inflammation that can lead to heart attacks, strokes, and other potentially life-threatening events. The breakthrough involving Kruppel-like factor (KLF) 15 is the latest in a string of discoveries from the laboratory of professor of medicine Mukesh K. Jain, M.D., F.A.H.A., that involves a remarkable genetic family. Kruppel-like factors appear to play prominent roles in everything from cardiac health and obesity to metabolism and childhood muscular dystrophy. School of Medicine instructor Yuan Lu, M.D., a member of Dr. Jain’s team, led the study involving KLF-15 and its role in inflammation, which was published online on Sepember 3, 2013 in the Journal of Clinical Investigation. Dr. Lu and colleagues observed that KLF-15 blocks the function of a molecule called NF-kB, a dominant factor responsible for triggering inflammation. This finding reveals a new understanding of the origins of inflammation in vascular diseases, and may eventually lead to new, targeted treatment options. “It had been suspected that smooth muscle cells were related to inflammation, but it hadn’t been pinpointed and specifically linked to disease,” said Dr. Jain, Ellery Sedgwick Jr. Chair and director, Case Cardiovascular Research Institute at Case Western Reserve School of Medicine. Dr. Jain also is chief research officer for the Harrington Heart & Vascular Institute at University Hospitals Case Medical Center. “This work provides cogent evidence that smooth muscle cells can initiate inflammation and thereby promote the development of vascular disease.” Smooth muscle cells are only one of two major cell types within blood vessels walls. The other cell type, endothelium, has traditionally taken the blame for inflammation, but Dr.