Ascending KLFs in cardiovascular biology.

Cardiac transcription factor biologists have spent many years identifying transcription factors that function as critical regulators of important cellular processes; however, the challenges in understanding cardiac transcriptional regulatory networks have been formidable. The cardiovascular system is a complex organ system in which component muscle cells must interact with other cells in a coordinated fashion to generate and maintain the heart and vasculature. Within the heart, muscle cells contract to circulate the blood, while specialized muscle cells are required for generation of the heartbeat and electrical propagation of coordinated contractile signals. In the vasculature, vascular smooth muscle cells (VSMCs) maintain vascular tone but also undergo phenotypic changes including proliferation, migration, and conversion from a contractile, differentiated state to a more synthetic, dedifferentiated state in response to injury. At the molecular level, various transcription factors within these cells coordinate gene expression patterns to enable them to perform these various roles. Linking transcription factors to the complex and varied behaviors of cardiac and smooth muscle cells has challenged transcription factor biologists for many years. Disruptions within these transcriptional networks can lead to extensive functional deficits. Studies on the Kruppel-like factors (KLFs) provide many instructive examples. The KLFs comprise a family of zinc finger transcription factors whose members play important roles in cardiovascular tissues, as highlighted in this issue of the Journal [1]. In this review, the authors provide a concise and timely update on the biology of KLFs in cardiac, smooth, and skeletal muscle. These factors are numerous, comprising 18 members to date, and are functionally diverse, serving as either ubiquitous or tissue-restricted transcriptional repressors or activators that interact with numerous protein partners.