Physical State of Lipids and Foreign Substances Producing Atherosclerosis

Abstract

Evidence is presented in favor of the hyper-and macrochylomicronemia theory of atherosclerosis. The primary factor and sine qua non in atherosclerosis appears to be the presence in the circulating blood of coarsely suspended colloidal particles larger than those of normal plasma and composed of, or containing a substance fairly resistant to the resorptive and removal mechanisms of the arterial intima. Local intimal permeability and intravascular pressure are secondary factors that determine the local influx of plasma-derived lymph and thus determine the distribution of the lesions in the vascular tree. Increased local permeability, or hypertension, may cause increased deposition, but only when hyper- and macrochylomicronemia exists. The postprandial period after a fat-rich meal is the only time that normal plasma contains large amts. of coarsely particulate matter. Atherosclerosis results because: (1) oil and water do not mix, so that fats and oils in plasma must be carried in molecular complexes or stabilized colloidal particles; (2) fats absorbed from the intestine are carried as much larger particles; (3) the reticuloendothelial cells in the intima, plus the barrier action of the internal elastic membrane, are the responsible functional components of the mechanism of deposition and retention of those large particles that are forced into the intimal tissue spaces with the lymph. The normal plasma lipids and proteins pass through the intima. The large lipid particles in sustained or alimentary hyperlipemia are treated as particulate foreign bodies and are arrested, phagocytosed, and entrapped in the intima. In conclusion, fat-rich meals produce the temporary appearance of large lipid particles, cause the defense mechanisms of the intima to retain some of the particles, and thus gradually build up the full picture of stenotic and occlusive arterial disease.