Elyse Di Marco, Stephen P. Gray, Karin Jandeleit-Dahm
Abstract
A central mechanism driving vascular disease in diabetes is immune cell-mediated inflammation. In diabetes, enhanced oxidation and glycation of macromolecules, such as lipoproteins, insults the endothelium, and activates both innate and adaptive arms of the immune system by generating new antigens for presentation to adaptive immune cells. Chronic inflammation of the endothelium in diabetes leads to continuous infiltration and accumulation of leukocytes at sites of endothelial cell injury. We will describe the central role of the macrophage as a source of signaling molecules and damaging by-products which activate infiltrating lymphocytes in the tissue and contribute to the pro-oxidant and pro-inflammatory microenvironment. An important aspect to be considered is the diabetes-associated defects in the immune system, such as fewer or dysfunctional athero-protective leukocyte subsets in the diabetic lesion compared to non-diabetic lesions. This review will discuss the key pro-inflammatory signaling pathways responsible for leukocyte recruitment and activation in the injured vessel, with particular focus on pro- and anti-inflammatory pathways aberrantly activated or repressed in diabetes. We aim to describe the interaction between advanced glycation end products and their principle receptor RAGE, angiotensin II, and the Ang II type 1 receptor, in addition to reactive oxygen species (ROS) production by NADPH-oxidase enzymes that are relevant to vascular and immune cell function in the context of diabetic vasculopathy. Furthermore, we will touch on recent advances in epigenetic medicine that have revealed high glucose-mediated changes in the transcription of genes with known pro-inflammatory downstream targets. Finally, novel anti-atherosclerosis strategies that target the vascular immune interface will be explored; such as vaccination against modified low-density lipoprotein and pharmacological inhibition of ROS-producing enzymes.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Unspecified
2
3%
Other
6
10%
Unknown
17
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 September 2023.
All research outputs
#8,169,616
of 25,922,020 outputs
Outputs from Frontiers in endocrinology
#2,417
of 13,316 outputs
Outputs of similar age
#81,063
of 291,748 outputs
Outputs of similar age from Frontiers in endocrinology
#42
of 210 outputs
Altmetric has tracked 25,922,020 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 13,316 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 291,748 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 210 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.
