Anoïkis is defined as programmed cell death induced by the loss of cell/matrix 
interactions. Adhesion to structural glycoproteins of the extracellular matrix 
is necessary for survival of the differentiated adherent cells in the 
cardiovascular system, including endothelial cells, smooth muscle cells, 
fibroblasts, and cardiac myocytes. Adhesion is also a key factor for the 
differentiation of mesenchymal stem cells. In particular, fibronectin is 
considered a factor of survival and differentiation for many adherent cells. 
Adhesion generates cell tensional integrity (tensegrity) and repression of 
apoptotic signals, whereas detachment has the opposite effect. Anoïkis plays a 
physiological role by regulating cell homeostasis in tissues. However, anoïkis 
can also be involved in pathological processes, as illustrated by the resistance 
to anoïkis in cancer and its enhancement in degenerative tissue remodeling. 
Extracellular mediators of anoïkis include matrix retraction, leading to loss of 
tensegrity in fibroblasts, pharmacological disengagement of integrins by 
RGD-like peptides and fragments of fibronectin, and focal adhesion disassembly 
by fragments of thrombospondin, plasminogen activator-1, and 
high-molecular-weight kininogen. In addition to binding of the RGD peptide by 
integrins, the engagement of the heparin binding sites of adhesive glycoproteins 
with glycosaminoglycans on the cell surface is also involved in the prevention 
of cell detachment-induced apoptosis. Proteases able to degrade adhesive 
glycoproteins, such as fibronectin, induce anoïkis of vascular adherent cells. 
Active proteases can either be secreted directly by inflammatory cells, as 
elastase and cathepsin G by polymorphonuclear leukocytes, chymase and tryptase 
by mast cells, and granzymes by lymphocytes, or generated from circulating 
zymogens by activation in close contact with the cells. This is the case for the 
pericellular conversion of plasminogen to plasmin, which degrades fibronectin 
and induces anoïkis of smooth muscle cells. Involvement of proteases has also 
been proposed in the apoptotic response of cultured adherent cells to serum 
starvation. Anoïkis is probably involved in pathological remodeling of 
cardiovascular tissues, including cardiac myocyte detachment in heart failure, 
deendothelialization and plaque rupture in atherosclerosis, and smooth muscle 
cell disappearance in aneurysms and varicose veins. The absence of cell adhesion 
and growth resulting from cleavage of adhesive proteins also represents a major 
impediment to cellular healing, including the absence of cell recolonization of 
proteolytically injured tissue and the low efficacy of cell transplantation. 
However, the exact role of anoïkis in cardiovascular pathologies remains to be 
further defined.