Cellular Mechanisms in the Response of the Arterial Wall to Injury and Repair

Abstract

This synopsis emphasizes the inappropriateness of a "single stimulus-single response" approach in understanding the response of the arterial wall to injury and repair. The outcome of any injurious stimulus is a series of interactive cascades among the endogenousand exogenous cellular and non-cellular components of the arterial wall, and the cellular and non-cellular elements of the blood. Both genetic and hemodynamic factors can further influencethis response. The more prominent of the cellular and non-cellular components have beendiscussed.These include: I) the vascularendothelium, its dynamic interaction with macromolecules and formed elements of the blood, its role in the transport of plasma proteins, its influenceon the function of arterial smooth muscle cellsand the recruitment of blood-born monocytes; 2) the arterial smooth muscle cell, its role in the vasomotor function of the artery wall, arterial repair and reconstruction, metabolism of lipids and the secretion of cytokines regulating monocyte recruitment; 3) the mononuclear phagocyte, its role in arterial debridement, metabolism of modified LDLs, a precursor of the cholesteryl ester-rich foam cell, and the secretion of neutral hydrolases, bioactive lipids and cytokines; 4) lymphocytes, as mediators of the inflammatoryresponseand possibleautoimmune reactions;5)platelets, their rolesin hemostasis,thrombosis, atherogenesis, and the repair processand 6) plasma LDLs, their oxidative modification by cells of the vessel walland their roles in the injury process.The interactive processes among arterial and circulatingcomponents in both injury and repair is emphasized.

Activated PMNs lead to oxidative stress on chondrocytes: A study of swine knees

“…This cellular population dramatically changes during HA when PMNs increase markedly (about 5 × 10 6 -10 7 /mL). These cells produce ROS, when activated by various proinflammatory mediators (Røkke et al 1989, Botha et al 1995, which are released from endothelial cells and locally-recruited platelets after intraarticular vascular injury (Schwartz et al 1989). Several investigators have studied the damage to cartilage matrix and chondrocytes caused by activated PMNs, which are thought to augment the degradation of elastase (Weiss and Regiani 1984).…”

Rapid leukocyte activation following intraarticular bleeding

“…These cells have the ability to produce catabolic enzymes, cytokines, and reactive oxygen species following activation by different proinflammatory mediators such as platelet activating factor, thromboxan-A2, and leukotriens (LTB4). 15,16 These activators are released from the endothelial cells and from the locally recruited platelets 17 as a consequence of the intraarticular vascular injury. 18 However, the effect of supposed inflammatory mediators on leukocytes has not been investigated so far.…”

In vitro Inhibition by Defibrotide of Monocyte Superoxide Anion Generation: A Possible Mechanism for the Antithrombotic Effect of a Polydeoxyribonucleotide-Derived Drug

“…These cells are an important source of 2 major prothrombotic mechanisms, PCA and O2 [19][20][21], In addition, a recent report showed that D affects the O 2 generation by granulocytes [22], Therefore, we suspected that the antithrombotic effectiveness of D might involve a direct effect on monocytes. Our data indicate that the drug weakly af fects the generation of monocyte PCA, while it has the potential to inhibit the O2 genera tion in response to stimuli that affect cal cium movements.…”

“…Thus, other directions were explored. Current evi dence indicates that monocytes/macrophages play a major role in hemostasis and thrombosis through their ability to express procoagulant activity and generate oxygen free radicals O 2 [19][20][21]. Together with the information that D affects the generation of superoxide anion by granulocytes [22], this concept prompted us to evaluate whether D had any effect on monocytes, and the present paper reports the relevant data of the study.…”