In Hypercholesterolemia, Lower Peripheral Monocyte Count Is Unique Among the Major Predictors of Atherosclerosis

Abstract

Many studies have shown that enhanced monocyte adherence is an important factor in the initiation of atherosclerosis. Because the relationships between circulating monocyte count and atherosclerosis or its major predictors have received little attention, we conducted this study with the aim of clarifying these relationships. The study included 409 men and women who underwent a carotid artery duplex study and white blood cell analysis (Sysmex Cell Counter) during a 2-day health check at our hospital in 1994. We found no correlation between preexisting carotid atherosclerosis and monocyte count. After adjustment for age and sex, hypercholesterolemia, among the major predictors of atherosclerosis, showed a unique correlation with both lower monocyte count and percentage (P < .001, P < .0001, respectively), whereas smoking was correlated with a higher monocyte count (P < .001). There was a slight but nonsignificant increase in monocyte count in hypertension, diabetes, and hypertriglyceridemia. Our results imply that: (1) hypercholesterolemia has a strong, peripheral monocyte-reducing effect, probably due to direct enhancement of monocyte adhesion to the endothelium, which subsequently initiates the atherosclerotic process, and (2) the mechanisms of other predictor(s)-induced atherosclerosis may be quite different from that of hypercholesterolemia. Another possible explanation for the inverse correlation between monocyte count and serum cholesterol level is that decreased monocyte levels might lead to hypercholesterolemia because of decreased uptake of cholesterol from the plasma by less monocyte-derived macrophages. The reasons why preexisting carotid atherosclerosis did not correlate with monocyte count are also discussed.

Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF-1:CXCR4 axis

“…5,6,40 Moreover, patients with hypercholesterolemia present with thrombocytosis and elevated leukocyte counts, specifically of lymphocytes and neutrophils. 44 The mechanistic basis for the hematopoietic effects of cholesterol, namely its effects in the BM microenvironment, has not been established.We developed a model of murine hypercholesterolemia induced by a high-cholesterol diet, after which mice present elevated total cholesterol levels and a HDL-LDL inversion. Similar to patients with hypercholesterolemia, high-cholesterol mice present with increased lymphocytes (lymphocytosis), neutrophils (neutrophilia) and thrombocytosis, and also increased mobilization of HPCs.…”

“…5,6,40 Moreover, patients with hypercholesterolemia present with thrombocytosis and elevated leukocyte counts, specifically of lymphocytes and neutrophils. 44 The mechanistic basis for the hematopoietic effects of cholesterol, namely its effects in the BM microenvironment, has not been established.…”

Inverse Relationship Between Adherenceto the Mediterranean Diet and Serum Cystatin C Levels

“…In fact, the mono- cyte count in blood has been found to be a better cross-sectional marker of plaque presence than hs-CRP, interleukin-6 and WBC (22). Monocyte count has recently been demonstrated to be an independent predictor of future plaque formation (23). There is evidence that elastolytic cysteine proteases and their inhibitors, an important one being cystatin C, are involved in the pathogenesis of atherosclerosis.…”

Circulating CD14⁺CD16⁺ Monocyte Subsets as Biomarkers of the Severity of Coronary Artery Disease in Patients With Stable Angina Pectoris

“…Patients with MVD presented a higher Gensini score among the 3 groups (non-CAD, 6.0 (Figure 2A). Although no significant differences were seen among the 3 groups in terms of peripheral total monocyte counts, CD14 + CD16 + monocyte counts were significantly higher in patients with MVD (84 [58-120] cells/μl) than in those with SVD (vs. 47 cells/μl, P<0.001) or without CAD (vs. 28 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] cells/μl, P<0.001) (Figure 2B). However, CD14 + CD16 − monocyte counts were not significantly different among the 3 groups.…”