Coronary atherosclerosis severity is closely associated with decreased GLP-1R positivity among CD16+ pro-inflammatory and patrolling monocyte subsets

Olga Bloch; Alex Blatt; Michael Y Appel; Gilad Ben Yehudah; Dror Cantrell; Michael Goldberg; Itamar Love; Haitham Abu Khadija; Micha J Rapoport

doi:10.1016/j.athplu.2021.10.001

Coronary atherosclerosis severity is closely associated with decreased GLP-1R positivity among CD16⁺ pro-inflammatory and patrolling monocyte subsets

Atheroscler Plus. 2021 Oct 13:46:15-19. doi: 10.1016/j.athplu.2021.10.001. eCollection 2021 Dec.

Authors

Olga Bloch¹, Alex Blatt^{2

3}, Michael Y Appel⁴, Gilad Ben Yehudah⁵, Dror Cantrell⁶, Michael Goldberg^{4

7}, Itamar Love⁶, Haitham Abu Khadija^{2

3}, Micha J Rapoport^{1

6}

Affiliations

¹ Diabetes & Autoimmunity Research Laboratory, Yitzhak Shamir Medical Center Affiliated to Sackler Medical School Tel Aviv University, Zerifin, 70300, Israel.
² Heart Center, Kaplan Medical Center, Rehovot, Israel.
³ Affiliated with the Hebrew University, Jerusalem, Israel.
⁴ Institute of Allergy, Immunology and Pediatric Pulmonology, Yitzhak Shamir Medical Center Affiliated to Sackler Medical School Tel Aviv University, Zerifin, 70300, Israel.
⁵ Bacteriology Laboratory, Yitzhak Shamir Medical Center Affiliated to Sackler Medical School Tel Aviv University, Zerifin, 70300, Israel.
⁶ Department "C" of Internal Medicine, Yitzhak Shamir Medical Center Affiliated to Sackler Medical School Tel Aviv University, Zerifin, 70300, Israel.
⁷ Department of Pediatrics, Sackler School of Medicine, Tel-Aviv University, Israel.

Abstract

Background and aims: Glucagon Like Peptide-1 Receptor (GLP-1R) activation reduces pro-inflammatory responses of human monocytes, their accumulation in the vascular wall and foam cell formation inhibiting atherosclerogenesis. This suggests that reduction of circulating GLP-1-1R positive monocytes may have pro-atherogenic effects. It is unknown whether different CD14/CD16 monocytes subsets display GLP-1R and whether their relative proportions correlate with atherosclerosis severity. We evaluated the association between GLP-1R positivity in different CD14/CD16 monocyte subsets and coronary atherosclerosis severity.

Methods: Relative amounts of classical (CD14+/CD16-), intermediate pro-inflammatory (CD14+/CD16+) and non-classical patrolling (CD14-/CD16+) subsets of total circulating monocytes and the proportions of GLP-1R positive monocytes in these subsets were determined in 13 control subjects and 10 dyslipidemic ischemic heart disease (IHD) patients with severe angiographic proven coronary atherosclerosis using flow cytometry analysis. Atherosclerosis severity was calculated by SYNTAX score.

Results: In univariable analysis, severe atherosclerosis was associated with decreased proportion of classical monocytes and two fold increased CD16⁺ pro-inflammatory and patrolling subsets as compared with controls (p = 0.01, p = 0.02 and p = 0.01, respectively). Frequency of GLP-1R positive monocytes was decreased in both CD16⁺ subsets (p = 0.02 and p = 0.05, respectively) and negatively correlated with atherosclerosis severity (r = -0.65, p = 0.005 and r = -0.44, p = 0.05, respectively).

Conclusions: Increased skewing of the classical monocyte population toward CD16⁺ pro-inflammatory and patrolling subsets accompanied by decreased in GLP-1R positivity are associated with coronary atherosclerosis severity in IHD patients with dyslipidemia. Although the effect of potential confounders cannot be ruled out, our data suggest that failure of GLP-1R-dependent anti-inflammatory/anti-atherogenic control results in innate immune system dysfunction and can promote atherosclerogenesis.

Keywords: CD14/CD16 monocyte subsets; Flow cytometry; GLP-1R; SYNTAX score; Severe atherosclerosis.