Lipid rafts: integrated platforms for vascular organization offering therapeutic opportunities

Abstract

Research on the nanoscale membrane structures known as lipid rafts is relevant to the fields of cancer biology, inflammation and ischaemia. Lipid rafts recruit molecules critical to signalling and regulation of the invasion process in malignant cells, the leukocytes that provide immunity in inflammation and the endothelial cells that build blood and lymphatic vessels, as well as the patterning of neural networks. As angiogenesis is a common denominator, regulation of receptors and signalling molecules critical to angiogenesis is central to the design of new approaches aimed at reducing, promoting or normalizing the angiogenic process. The goal of this review is to highlight some of the key issues that indicate the involvement of endothelial cell lipid rafts at each step of so-called 'sprouting angiogenesis', from stimulation of the vascular endothelial growth factor to the choice of tip cells, activation of migratory and invasion pathways, recruitment of molecules that guide axons in vascular patterning and maturation of blood vessels. Finally, the review addresses opportunities for future studies to define how these lipid domains (and their constituents) may be manipulated to stimulate the so-called 'normalization' of vascular networks within tumors, and be identified as the main target, enabling the development of more efficient chemotherapeutics and cancer immunotherapies.

Recent progress on lipid lateral heterogeneity in plasma membranes: From rafts to submicrometric domains

“…Besides temperature, cholesterol and Cer are two lipids requiring a thorough consideration in the context of phase separation. Cholesterol is a key component of membrane biology and the concept of its clustering into membrane domains is attractive to explain its different functions including (i) membrane fluidity via lipid ordering; (ii) membrane deformability by modulation of PM protein interactions at the interface with cortical cytoskeleton [52]; (iii) formation and stabilization of nanometric lipid assemblies, rafts and caveolae [40, 53], as signaling platforms [54-56]; and (iv) phase coexistence in artificial membranes [57-59]. Fig.…”

Cholesterol segregates into submicrometric domains at the living erythrocyte membrane: evidence and regulation

“…In contrast, cholesterol transbilayer distribution remains unclear; several studies, however, reached the same conclusion that a significant part (50-75 %) is distributed in the inner leaflet [5,6]. Membrane cholesterol plays key regulatory roles including (1) membrane fluidity via lipid ordering; (2) membrane deformability by modulation of plasma membrane protein interactions at the interface with cortical cytoskeleton [7]; (3) formation and stabilization of nanometric lipid assemblies, rafts and caveolae [2,4], as important signaling platforms [8][9][10]; and (4) phase coexistence in artificial membranes [11][12][13]. Cholesterol is, thus, a key component of membrane biology and the concept of its clustering into membrane domains is attractive to explain its different functions.…”

Alteration of actin dependent signaling pathways associated with membrane microdomains in hyperlipidemia

“…Integrin signaling is important as well for the control of Rho activity and can be modulated through mechanical changes in the cytoskeleton [ 85 ]. Also, it has been demonstrated that lipid rafts are mediating growth cone guidance in the angiogenetic process, through localized assembly of receptor-ligand interactions, the afterwards cytoskeletal rearrangement and local protein synthesis, including Src family kinases and Rho GTPases [ 86 ].…”