Relationship between Circulating Inflammatory Monocytes and Cardiovascular Disease Measures of Carotid Intimal Thickness

Abstract

The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article Aims: Cardiovascular disease (CVD) remains the leading cause of death worldwide despite improvements in the treatment of atherosclerosis, an inflammatory disease and major underlying cause of CVD. Monocytes, an innate immune cell type, are linked to CVD progression; however, given their heterogeneity, the association between distinct monocyte subsets and increased risk of CVD remains unclear. This study investigated the association between peripheral monocyte subpopulation numbers and carotid intima-media thickness (cIMT), a sensitive measure of CVD risk, in a cohort of adults recruited from the general population. Methods: We used clinical data and peripheral blood mononuclear cell (PBMC) specimens from 67 individuals. cIMT was measured by high-resolution, B-mode, ultrasound images of the right carotid artery. PBMCs were stained with conjugated monoclonal antibodies to define monocyte subpopulations based on CD14 and CD16 co-expressions into classical (CD14 CD16), intermediate/inflammatory (CD14 CD16), and non-classical/ patrolling (CD14 low/ CD16) monocytes. Results: We found a higher intermediate monocyte count was significantly correlated with increased right common carotid artery (RCCA) and right carotid bifurcation (RBIF) intima-media thickness (IMT) (p 0.004 and 0.006, respectively), even after adjusting for CVD-associated clinical data (p 0.006 and 0.004, respectively). Conclusion: Our study demonstrated a strong correlation between inflammatory monocyte counts and cIMT. These results suggest that, in the general population, there is a relationship between intermediate monocyte expansion and elevated predictors for CVD risk, and intermediate monocytes may be involved in the development of atherosclerosis and metabolic diseases. Strategies targeting inflammatory monocytes may be needed to slow CVD progression. role in atherosclerotic plaque formation 1, 3). Based on CD14 and CD16 surface co-expression, monocytes are classified into three different subsets: classical (CD14 CD16), intermediate or inflammatory (CD14 CD16), and non-classical or patrolling (CD14 low/ CD16) 4). Existing studies have demonstrated monocytes' roles in various disorders, including those that are associated with CVD. Higher levels of classical monocytes have been correlated with insulin resistance, a metabolic disorder closely related to

Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells

“…Based on these markers, 5 of the 8 classical monocyte subsets were called ( Figure 2C ) and related to subsets described by mass cytometry. 78 Intermediate CD14+CD16+ monocytes (INT) have been considered pro-inflammatory by several investigators 79–83 and are known to be increased in people with HIV 84, 85 and with CVD. 82, 86, 87 All intermediate monocytes highly expressed the inflammation-induced costimulatory molecule CD86 ( Figure 2C ).…”

“…Tissue factor expression on monocytes has previously been shown to be increased in HIV+ subjects. [45] Intermediate monocytes are considered pro-atherogenic, [44] and tissue factor expression provides a plausible reason for this. We found that in INT2 and INT3, the inflammatory chemokines CCL3 and In CD4T cells clusters 1, 2 and 8, IL-32 was highly significantly increased by CVD, which was reversed by cholesterol lowering in CD4T1 and 2 (Figure 6).…”

Chronic Kidney Disease and Atherosclerosis: An Important Implication of Carotid Intima-Media Thickness

“…Many factors, including increased production of proinflammatory cytokines, oxidative stress, acidosis, altered lipid metabolism, accumulation of uremic toxins such as indoxyl sulfate, and gut microbiota dysbiosis, contribute to the setting of inflammatory status of CKD. Relationship between circulating inflammatory monocytes and carotid IMT has also been recently reported 7) . Thus, inflammatory status of CKD might promote the accelerated increase of carotid IMT.…”

Associations of Baseline and Changes in Leukocyte Counts with Incident Cardiovascular Events: The Dongfeng-Tongji Cohort Study

“…Conversely, limited prospective studies have reported conflicting relation of differential leukocyte counts with CVD incidence. Several studies demonstrated that higher neutrophil count increased the risk of CVD incidence [27][28][29] , and monocyte count was also reported as a risk factor for CVD, CHD, and IS 15,30,31) . However, eosinophil and lymphocyte counts were reported to be inversely associated with the risk of CVD 32) .…”