Effect of the inhibition of platelet function on the development of the primary atherogenic lesion in rats on a fat- and cholesterol-rich diet.

The involvement of arterial smooth muscle cells in the development of atherogenic lesions following de-endothelialization and platelet-vessel wall interaction was described in detail by Ross et al. (1977). Bourgain & Six (1974) described a method for local de-endothelialization over a small area in a branch of the mesenteric artery of the male white Wistar rat. The vessel wall reaction to the endothelial cell loss was investigated in detail by Potvliege & Bourgain (1976). The reactive pattern following de-endothelialization includes both a marked hypertrophy of the smooth muscle cells, and, if induced at the site of bifurcation, is further accompanied by migration of smooth muscle cells into the subintimal layer (Potvliege & Bourgain 1980). Administration of a fat- and cholesteral-rich diet markedly increased these phenomena (Potvliege & Bourgain 1982).

The effect of a fat-rich diet on the ultrastructure of mesenteric arteries of the rat and their reaction to local desendothelialization.

By comparison with the previously described results of similar experiments performed on normal rats (Potvliege and Bourgain, 1976, 1980), it was observed that with a fat-rich diet the endothelium contained a greater number of Weibel-Palade bodies and that there was an increased tendency for blood monocytes to stick to the endothelium as well as for platelets to form, small, non-adherent aggregates particularly at sites of arterial branching opposite intimal cushions. The intimal cushions were larger and they reacted to local thrombogenic treatment by greater and more prolonged myointimal growth. In addition, although their endothelial lining did not become detached, individual cells showed signs of degeneration. These changes are interpreted as indicating that a fat-rich diet enhances atherogenesis at points of greater haemodynamic stress by locally increasing intraluminal platelet aggregation and endothelial-cell degeneration. These 2 ever-recurring events favour, in the former case, a slow but steady liberation of platelet factors, and, in the latter, an easier penetration into the artery wall of mitogenic substances which stimulate myointimal growth. The adhesion of monocytes to the endothelium may represent a first step towards their migration into the intima where, at a later stage, they may become transformed into foam cells, thus completing the atherogenic cycle.

Microdeposition of amyloid in the joints.

The distribution of amyloid in various organs, including the hip and the sternoclavicular joints, was systemically investigated in a prospective necropsy study of 91 unselected individuals whose median age was 70 years. The overall incidence of amyloid microdeposits in both joints was 56%. Their presence correlated significantly with age only. The deposition began earlier in the sternoclavicular joint, where the fibrocartilaginous disc was almost exclusively affected. The myocardium was the next most frequently affected organ, with an incidence of 12.2%. Minor amyloidosis of the articular tissues had no significant clinical counterpart, neither was it associated with any particular disease. It seemingly represents a localised and isolated degenerative phenomenon, whose morphological aspects invite speculation about the pathogenic role of long-lasting mechanical stress.

The wall reaction to electric micro-injury at branching sites of mesenteric arteries of the rat: an electron microscopic study of intimal cushions.

Intimal cushions consist of small bundles of longitudinally oriented smooth-muscle cells (SMC) which are interposed between the endothelium and the lamina elastica interna (LEI) of arteries. They are consistently present on the mouths of artherial branchings, at sites of haemodynamic stress. In structure and location, they closely resemble early artherosclerotic lesions. In previous experiments, we studied the local consequences of a standardized microthrombosis induced in non-branching segments of mesenteric arteries of rats. In this experimental model, the endothelium gets reconstituted within 24 h while in the underlying media the SMC exhibit a marked growth reaction which reaches a peak on the third day and eventually terminates by the sixth day with full restitution to normal. In the present work, the experiment was repeated at sites of arterial branchings. It was seen that in this location the SMC growth reaction was greatly enhanced and led to a marked increase in size of the intimal cushions. In addition their endothelial lining, although reconstituted, showed a persistent tendency to segmental breakdown. These results support the view that intimal cushions develop as a consequence of local haemodynamic stress which, by causing endothelial-cell loss, triggers off the sequence of blood-platelet adhesion, aggregation and release of mitogenic factors, the latter being ultimately responsible for an ever-recurring stimulation of myointimal growth. The same mechanisms are likely to operate in atherogenesis.

Thrombosis induced in vivo in the femoral artery of rats. An electron microscopic study of myointimal growth.

Minor injury and thrombosis, induced in a short arterial segment by the successive applications of a weak electric current and a dilute solution of ADP, is followed by rapid reconstitution of the endothelium and protracted growth of the medial smooth-muscle cells (SMC). Previous investigations of their early stages have shown that both processes are platelet-dependent. In the present investigation the arterial-wall reaction was followed up to the eighth day. By that time the growth of SMC had abated and the artery wall had regained a normal structure. Locally repeating the electric treatment consistently caused an infiltration of the inner media by blood elements, notably platelets. Rupture of the lamina elastica interna (LEI) was an additional feature in one out of 6 repeatedly treated arteries. Despite greater initial damage, repair of the artery wall proceeded normally in the majority of cases. In 2 out of 7 arteries, however, the SMC of the inner media exhibited cytologic evidence of still active stimulation and disordered growth on the eighth day. In one of the 2 arteries, the LEI had ruptured over wide areas where myointimal thickening was observed. Intimal denudation was brief in all cases so that the release of mitogenic factors by insudated platelets and the disruption of the LEI are more likely to have been the effective agents of myointimal growth.