Targeting Wnt-Frizzled signaling in cardiovascular diseases

Abstract

Wnts are secreted glycoproteins implicated in biological processes ranging from embryonic cardiac development to uncontrolled cell proliferation in diseased conditions. Cardiovascular disease is a major cause of morbidity and mortality worldwide. Phenotypic modulation of vascular smooth muscle cells, migration and proliferation in intimal layer and increased extracellular matrix production are some of the known hallmarks of cardiovascular pathologies. Heterogeneity associated with the binding of Wnts to their transmembrane receptors, Frizzled, and coreceptors low density lipoprotein-receptor-related protein is indeed intriguing. Nuclear-cytoplasmic shuttling of beta-catenin and activation of transcriptional factors, lymphoid enhancer factor and T cell activation factor leading to target gene activation has remained elusive. Our review highlights the emerging role of Wnt-Frizzled signaling in cardiovascular diseases. Overall, the pathway appears to be an attractive therapeutic target in identifying susceptible individuals at risk of developing restenosis/other vascular pathologies in the near future.

Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis

“…Defective Wnt signaling can result in various cardiac and vascular abnormalities. Moreover, in other studies, it was indicated that Wnt signaling is involved in cardiovascular diseases coupled with ion channels and cardiac hypertrophy [35,36]. In the present study, b-catenin expression was detected in human infarct hearts and in diseased animal model hearts.…”

Increment of HFABP Level in Coronary Artery In-Stent Restenosis Segments in Diabetic and Nondiabetic Minipigs: HFABP Overexpression Promotes Multiple Pathway-Related Inflammation, Growth and Migration in Human Vascular Smooth Muscle Cells

“…Induction of these pathways is also verified in ISR versus non-ISR tissue. Substantial evidence indicates that the Wnt, HH, BMP and Notch pathways play a role in the physiological differentiation and homeostasis of epithelial cells, and that the alterations of these pathways contributes to the pathophysiology of skeletal and cardiovascular diseases and tumorigenesis [17,18,19,20,21,22,23,24]. These pathways also appear to have cross-talk among them [25,26,27,28,29,30,31].…”

FoxO Proteins in the Nervous System

“…This increased expression of Wnt1 appears to be protective since loss of Wnt1 translates into progressive spinal cord injury [ 198 ], impaired neurogenesis [ 199 ], and apoptosis [ 156 , 193 , 200 ]. Wnt1 signaling pathways can prevent cellular injury during experimental diabetes [ 28 , 201 ], ischemic brain injury [ 197 , 202 ], dopaminergic neuronal cell injury [ 179 , 189 , 195 , 203 ], toxic environments for microglia and other inflammatory cells [ 69 , 104 , 191 , 193 ], and neuronal synaptic dysfunction [ 204 ]. Wnt signaling can afford cellular protection against apoptotic cell death through the inactivation of FoxO proteins.…”