The role of prolactin/vasoinhibins in cardiovascular diseases

FIGURE 1. Vasoinhibins are produced from proteolytic cleavage of 23‐kDa PRL by several endogenous proteolytic enzymes, such as cathepsin D, matrix metalloproteinase (MMP), and bone morphogenetic protein‐1 (BMP‐1). 35 And vasoinhibins contain the NH2‐terminal part of the mature PRL protein but not the COOH‐terminal fragment. Prolactin (PRL) promotes angiogenesis, whereas vasoinhibins possess antiangiogenic property. The specific impact on vascular is shown in the figure. The solid line has an arrow to indicate the promoting effect, and the other line indicates the inhibiting effect.

FIGURE 2. pPRL (pituitary prolactin) is mainly synthesized and secreted by the lactotroph cells of the anterior pituitary, and this process is mainly regulated by dopamine and thyroid stimulating hormone releasing hormone (TRH) released in the hypothalamus. pPRL exerts a negative feedback effect on its own secretion by affecting dopamine secretion in the hypothalamous or direct action on lactotroph cells. PRL is also produced by autocrine and paracrine cells in numerous extrapituitary tissues (ePRL), such as immune cells and vascular endothelial cells. 85 Promotion is indicated by a solid line with arrow, and the other line indicates inhibition.

FIGURE 3. Signal pathways that may be involved in the combination of PRLR and PRL (prolactin): canonical Janus kinase 2 (JAK2)‐signal transducer and activator of transcription (STAT) pathway, mitogen‐activated protein kinase (MAPK) pathway, and phosphatidylinositol‐3‐kinase (PI3K)/Akt pathways. Signal transduction pathways are known to be activated in endotheliall cells by vasoinhibins. 39 The binding of vasoinhibins to its receptor and the recognition and localization of vasoinhibins are unknown, including increasing the expression of PAI‐1, activating Bcl Xs and/or NFkB, and blocking the stimulating effect of vascular endothelial growth factor (VEGF) on eNOS, RAS–MAPK pathway, or RAS–PAK1 pathway. Promotion is indicated by a solid line with arrow, and the other line indicates inhibition. IP3, inositol trisphosphate; PAI‐1, plasminogen activator inhibitor‐1; PLC, phospholipase C; u‐PA, urokinase‐type plasminogen activator.