Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation

https://science.sciencemag.org/content/sci/240/4852/622.full.pdf

Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

The proteoglycan superfamily now contains more than 30 full-time molecules that fulfill a variety of biological functions. Proteoglycans act as tissue organizers, influence cell growth and the maturation of specialized tissues, play a role as biological filters and modulate growth-factor activities, regulate collagen fibrillogenesis and skin tensile strength, affect tumor cell growth and invasion, and influence corneal transparency and neurite outgrowth. Additional roles, derived from studies of mutant animals, indicate that certain proteoglycans are essential to life whereas others might be redundant. The review focuses on the most recent genetic and molecular biological studies of the matrix proteoglycans, broadly defined as proteoglycans secreted into the pericellular matrix. Special emphasis is placed on the molecular organization of the protein core, the utilization of protein modules, the gene structure and transcriptional control, and the functional roles of the various proteoglycans. When possible, proteoglycans have been grouped into distinct gene families and subfamilies offering a simplified nomenclature based on their protein core design. The structure-function relationship of some paradigmatic proteoglycans is discussed in depth and novel aspects of their biology are examined.

/pdf/matrix-proteoglycans-from-molecular-design-to-cellular-2vn9t5k5g8.pdf

Matrix Proteoglycans: From Molecular Design to Cellular Function

Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety

The role of a local angiotensin system in the vascular response to arterial injury was investigated by administering the angiotensin-converting enzyme (CE) inhibitor cilazapril to normotensive rats in which the left carotid artery was subjected to endothelial denudation and injury by balloon catheterization. In control animals, by 14 days after balloon injury, the processes of smooth muscle cell (SMC) proliferation, migration of SMCs from the media to the intima, and synthesis of extracellular matrix produced marked thickening of the intima, with reduction of the cross-sectional area of the lumen. However, in animals that received continuous treatment with the CE inhibitor, neointima formation was decreased (by about 80 percent), and lumen integrity was preserved. Thus, the angiotensin-converting enzyme may participate in modulating the proliferative response of the vascular wall after arterial injury, and inhibition of this enzyme may have therapeutic applications to prevent the proliferative lesions that occur after coronary angioplasty and vascular surgery.

https://science.sciencemag.org/content/sci/245/4914/186.full.pdf

Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury.

A 70 percent reduction in the rate of blood flow through the common carotid artery in rabbits caused a 21 percent decrease in the diameter of this artery within 2 weeks. The smooth muscle relaxant papaverine did not attenuate the response; therefore, such reductions in diameter probably reflect a structural modification of the arterial wall rather than sustained contraction of smooth muscle. This arterial response to reduced blood flow was abolished when the endothelium was removed from the vessels. It appears that the endothelium is essential for the compensatory arterial response to long-term changes in luminal blood flow rates.

https://science.sciencemag.org/content/sci/231/4736/405.full.pdf

Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent

INTIMAL smooth muscle cell (SMC) proliferation dominates the early phase of healing after arterial endothelial injury1–6; what growth factors are responsible for this mitotic activity of an otherwise quiescent cell is not known. SMC growth in vitro is enhanced by platelet factors, insulin and lipoproteins7–11 and, according to some reports, can be diminished in vivo with various antiplatelet agents. Harker et al.6 have reported decreased myointimal thickening in homocystinaemic baboons treated with dipyridamole, and Friedman et al.11 and Moore et al.12 have reported suppression of SMC proliferation in the injured arteries of rabbits injected with anti-platelet serum. Intimal thickening was not diminished, however, in the injured carotid arteries of rats given various anti-platelet drugs13. Because the clotting system is inextricably linked to arterial injury and because thrombin is used to generate the platelet growth factor9 and may itself be a mitogen14,15, we speculated that heparin might inhibit myointimal thickening. We report here the use of heparin to suppress intimal SMC hyperplasia in a rat model of arterial endothelial injury and suggest possible mechanisms for the heparin effect.

Alerander W. Clowes

Papers

Suppression by heparin of smooth muscle cell proliferation in injured arteries