Inflammatory Cell Recruitment in Cardiovascular Disease

Abstract

Atherosclerosis, the main underlying pathology for myocardial infarction and stroke, is a chronic inflammatory disease of middle-sized to large arteries that is initiated and maintained by leukocytes infiltrating into the subendothelial space. It is now clear that the accumulation of pro-inflammatory leukocytes drives progression of atherosclerosis, its clinical complications, and directly modulates tissue-healing in the infarcted heart after myocardial infarction. This inflammatory response is orchestrated by multiple soluble mediators that enhance inflammation systemically and locally, as well as by a multitude of partially tissue-specific molecules that regulate homing, adhesion, and transmigration of leukocytes. While numerous experimental studies in the mouse have refined our understanding of leukocyte accumulation from a conceptual perspective, only a few anti-leukocyte therapies have been directly validated in humans. Lack of tissue-tropism of targeted factors required for leukocyte accumulation and unspecific inhibition strategies remain the major challenges to ultimately translate therapies that modulate leukocytes accumulation into clinical practice. Here, we carefully describe receptor and ligand pairs that guide leukocyte accumulation into the atherosclerotic plaque and the infarcted myocardium, and comment on potential future medical therapies.

Treatment With Suboptimal Dose of Benznidazole Mitigates Immune Response Molecular Pathways in Mice With Chronic Chagas Cardiomyopathy

“…Moreover, Bz (0.63 ± 0.30), PTX (0.69 ± 0.47), and Bz+PTX (1.37 ± 0.28) therapeutic strategies showed no regulation of CD19 expression ( Figure 6G ). Selectin, a glycoprotein from the cell adhesion molecules family ( Marchini et al., 2021 ), had shown decreased expression in our RT-qPCR TaqMan array profiling for the vehicle-treated group compared with the non-infected group. However, in the validation of individual samples, the expression of selectin increased in the vehicle-treated group (1.53 ± 0.25), when compared with the non-infected control (0.89 ± 0.15), and therapy with Bz (2.00 ± 0.42), PTX (1.48 ± 0.16) or the combined therapy with Bz+PTX (1.70 ± 0.22) have no impact in selectin expression in the heart tissue of chronically infected mice ( Figure 6H ).…”

The 3-Year Effect of the Mediterranean Diet Intervention on Inflammatory Biomarkers Related to Cardiovascular Disease

“…Leukocyte activation takes place by chemokines (monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T cells expressed and secreted (RANTES), interferon gamma-induced protein 10 (IP-10)) and chemokine receptors (CCR2, CCR5, CXCR2), which attract monocytes, neutrophils, dendritic cells (DCs) and T cells into the intima [ 5 , 8 , 9 , 10 , 11 ] and induce inflammasome activation (Nod-like receptor protein (NLRP) in macrophages [ 4 , 6 ]. This activation leads to the maturation of caspase-1 and the processing of its substrates, interleukin (IL)-1β and IL-18 [ 2 , 6 , 12 ], and finally IL-1β promotes the development of lipid plaque and also destabilizes it [ 6 , 13 ].…”

Trafficking of Mononuclear Phagocytes in Healthy Arteries and Atherosclerosis

“…Continuous inflammatory triggering by the persistent influx of apoB-containing lipoproteins causes a substantial monocyte recruitment within the first 1-2 weeks of hypercholesterolemia ( 16 , 78 , 79 ). The subendothelial inflammatory foci lead to the expression of adhesion molecules on activated endothelial cells and the secretion of chemokines, most importantly of CCL2/MCP-1, CX3CL1 and CCL5 ( 80 ) These factors are essential for the infiltration of primarily Ly6C high monocytes into the developing atherosclerotic plaque ( 81 , 82 ). Combined absence of all three chemokine-chemokine receptor pairs results in an almost complete inhibition of lesion development ( 82 – 84 ).…”