Stress and Atherogenesis: Smooth Muscle Cell Mitogenic Activity and other Biochemical Changes Associated with Sera of \"Stressed\" Subjects

The proliferation of smooth muscle cells in the arterial wall (VSMC) is considered to play a key role in the development of atherosclerosis. To investigate the possible contribution of "stress" (experimentally-induced) to this process, blood from healthy volunteers, ages 21 to 65, screened to exclude major risk factors for coronary heart disease, was assayed for mitogenic activity after the subjects were exposed to one of 2 "stress" conditions. These consisted of a cognitive task with superimposed verbal harassment (group 1), and the cognitive task without harassment (group 2). Mitogenic activity was determined by studying the growth stimulatory effects of PDGF-depleted plasma derived serum (PDS) from "stressed" subjects added to cultured VSMC, as measured by incorporation of radioactive thymidine into DNA or increase in cell number. In addition, changes in the steady state of the mRNA for the c-myc protooncogene were also assayed in VSMC by Northern blot analysis, using sera showing the greatest differential "pre/post stress" mitogenic activity. Blood pressure (BP), heart rate (HR), cortisol, and serum total and HDL cholesterol were also evaluated. All measurements were made immediately before (baseline) and after a 30 min interval. Analysis of the data revealed that there were 33% of subjects in group 1 with an increase of thymidine incorporation 15% or greater than baseline, versus 21% in group 2. The average increases were 45% and 30%. A higher percentage (35-42%) of subjects in group 1 responded with increases in systolic and diastolic blood pressure, compared to subjects in group 2 (15‌20%) the average in blood pressure was 10-15%. Similarly, more subjects (52%) in group 1 had an elevated (average 10-15%) serum cortisol, compared to the 42% in group 2 subjects. HR, total HDL cholesterol showed slight changes only. These results suggest that psychoactive factors may affect cardiovascular systems via rapid elicited rises in serum mitogenic activity for VSMC.