ABSTRACT
Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an extracellular signaling molecule by binding to and activating at least five known G protein-coupled receptors (GPCRs): LPA(1)-LPA(5). They are encoded by distinct genes named LPAR1-LPAR5 in humans and Lpar1-Lpar5 in mice. The biological roles of LPA are diverse and include developmental, physiological, and pathophysiological effects. This diversity is mediated by broad and overlapping expression patterns and multiple downstream signaling pathways activated by cognate LPA receptors. Studies using cloned receptors and genetic knockout mice have been instrumental in uncovering the significance of this signaling system, notably involving basic cellular processes as well as multiple organ systems such as the nervous system. This has further provided valuable proof-of-concept data to support LPA receptors and LPA metabolic enzymes as targets for the treatment of medically important diseases that include neuropsychiatric disorders, neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis, and cancer.
Subject(s)
Receptors, Lysophosphatidic Acid/classification , Receptors, Lysophosphatidic Acid/physiology , Animals , Cardiovascular Physiological Phenomena , Fibrosis , Humans , Immune System/physiology , Lysophospholipids/metabolism , Neoplasms/etiology , Nervous System Physiological Phenomena , Obesity/etiology , Receptors, Lysophosphatidic Acid/agonists , Receptors, Lysophosphatidic Acid/antagonists & inhibitors , Reproduction , Signal TransductionABSTRACT
Lysophosphatidic acid (LPA) is a small signaling lipid that is capable of stimulating a plethora of different cellular responses through the activation of its family of cognate G protein-coupled receptors. LPA mediates a wide range of biological effects in many tissue types that have been recently reviewed; however, its effects on vasculature development and function have received comparatively less examination. In this review, literature on the actions of LPA in three main aspects of vascular development (vasculogenesis, angiogenesis, and vascular maturation) is discussed. In addition, evidence for the roles of LPA signaling in the formation of secondary vascular structures, such as the blood brain barrier, is considered, consistent with significant roles for LPA signaling in vascular development, function, and disease.
