Krüppel-like factors (KLFs) are a subclass of the zinc-finger family of transcriptional regulators implicated in the regulation of cellular growth and differentiation and tissue development. The term Krüppel is a German word meaning “cripple.” This is based on the observation that Drosophila embryos homozygous for Krüppel die due to altered thoracic and anterior abdominal segments (1–3). Over the past 13 years, 17 mammalian KLFs have been identified and found to play important roles in diverse cell types. For example, the first mammalian KLF, termed erythroid Krüppel-like factor (EKLF/KLF1), was found to play a key role in β-globin gene synthesis and erythrocyte development (4, 5). Other family members have been shown to play critical roles in diverse processes ranging from epithelial cell differentiation, tumor cell growth, and bone formation (6–10). Recent studies also implicate an important role for these factors in cardiovascular biology (11, 12). In this chapter, we discuss published studies to date that support a critical role of lung Krüppel-like factor 2 (LKLF/KLF2) in endothelial biology.

IDENTIFICATION AND INITIAL CHARACTERIZATION OF KRÜPPELLIKE FACTOR-2

KLF2 was originally cloned in the Lingrel laboratory using a homology screening strategy (13). Subsequent gene targeting studies indicate an essential role for this factor in programming the quiescent phenotype of single-positive T cells and in lung development (14, 15). In addition, KLF2-/- mice exhibit abnormal blood vessel formation due to insufficient smooth muscle cell recruitment, which results in embryonic hemorrhage and death between embryonic (E) day 12.5 and 14.5(16). The latter observation suggested that KLF2 has an important role in vessel biology. Interestingly, it was shown that within the blood vessel wall, KLF2 expression was limited limited to endothelial cells (ECs) (16).