Abstract
Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T cell activation by binding to the PD-1 receptor. The general attributes of PD-L1’s immune-suppressive qualities and novel mechanisms on the barrier functions of vascular endothelium to regulate blood vessel-related inflammatory diseases are concisely reviewed. Though targeting the PD-1/PD-L1 axis has received immense recognition—the Nobel Prize in clinical oncology was awarded in the year 2018 for this discovery—the use of therapeutic modulating strategies for the PD-L1/PD-1 pathway in chronic inflammatory blood vessel diseases is still limited to experimental models. However, studies using clinical specimens that support the role of PD-1 and PD-L1 in patients with underlying atherosclerosis are also detailed. Of note, delicate balances in the expression levels of PD-L1 that are needed to preserve T cell immunity and to curtail acute as well as chronic infections in underlying blood vessel diseases are discussed. A significant link exists between altered lipid and glucose metabolism in different cells and the expression of PD-1/PD-L1 molecules, and its possible implications on vascular inflammation are justified. This review summarizes the most recent insights concerning the role of the PD-L1/PD-1 axis in vascular inflammation and, in addition, provides an overview exploring the novel therapeutic approaches and challenges of manipulating these immune checkpoint proteins, PD-1 and PD-L1, for suppressing blood vessel inflammation.
Highlights
The term “vasculitides” is a collective designation referring to any vascular-related ailments where inflammation commences, propels and advances at different zones of the blood vessel wall and the degree of inflammation is considered to be the principal risk factor in promoting the disease severity and the outcomes [1,2]
These include (i) coronary artery disease (CAD), where inflammatory plaques occur in the coronary arteries, which lessens the oxygen supply to the heart muscle and leads to myocardial infarction (MI) [16], (ii) peripheral artery occlusion disease (PAOD), where an inflammation occurs at extremities and prevails in the regions that are distal from the heart [17], and (iii) carotid stenosis (CS), where inflamed lesions occur in the carotid arteries of neck, which hinders the supply of oxygenated blood to the brain, leading to stroke [18]
Though we summarized the involvement of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) or PD-L2 molecules in the pathogenesis of the different primary vasculitides (Table 1), the key content of this review is majorly subjected to a deep-seated awareness and a knowledge acquisition on the role of the PD-L1/PD-1 axis in various pathomechanistic and clinical aspects of atherosclerotic blood vessel inflammatory diseases—in particular, CAD, PAOD, CS, MI and stroke
Summary
The term “vasculitides” is a collective designation referring to any vascular-related ailments where inflammation commences, propels and advances at different zones of the blood vessel wall and the degree of inflammation is considered to be the principal risk factor in promoting the disease severity and the outcomes [1,2]. Besides the primary blood vessel inflammatory diseases, the secondary vascular diseases are the major classified determinants for atherosclerosis in western countries, where the development of CVD is tightly linked to (i) the current industrialized economy that demands sedentary jobs and technology-driven culture demanding for longer work hours resulting in lack of physical and recreational activities, (ii) intake of a high-calorie diet with saturated fats and refined sugars, and (iii) change in the lifestyle, in particular, cigarette smoking habits irrespective of gender [21] These aforementioned risk factors in the modern world are majorly responsible for atherogenesis and other associated metabolic disturbances such as obesity, hypertension and type 2 diabetes mellitus which prevail in people with CVD [22,23]. Minimizing immune activation and preventing further damage the vessel wall human and mice
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