The dawn has come for new therapeutics to treat atherosclerosis: Targeting neuroimmune cardiovascular interfaces in artery brain circuits

Abstract

Atherosclerosis is the leading cause of mortality worldwide. However, regrettably, there are no treatment options that target the root causes of the disease, as its pathogenic mechanisms largely remain to be defined. Atherosclerosis has been viewed as a chronic inflammatory and unresolvable condition of all three arterial wall layers: Plaques develop in the inner intima layer of arteries leading to lumen narrowing and reduction of blood flow to downstream tissues, and when critical thresholds are breached, they cause heart attacks and strokes; smooth muscle cells in the media layer transdifferentiate into a synthetic and migratory phenotype and participate in artery remodelling by changing their transcriptome profile and secreting cytokines; and immune cells accumulate in the outer connective tissue coat of arteries, that is, the adventitia, andThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Genetic architecture of the HLA/MHC locus in cardiometabolic disease, severe mental illness, and related traits.

“…Neuroin ammation has been proposed as a mechanism connecting SMI and CMD, which is supported by growing evidence of neuroin ammatory control of vasculature (43). This work highlights candidate genes that might contribute to the neuroin ammatory mechanisms regulating CMD, however the different effects depending upon isoform, cellular location, cell type and in ammatory/metabolic environment means that clarifying their exact roles will take time.…”

Cardiovascular Brain Circuits

“…Recent progress to define a structural ABC 7,8,54 together with the better understood HBC 26,55,189,190 and rapid advances on the role of the immune system to direct both the ABC and the HBC 1,2,9,69,71,133,143,191 support the presence of a global CBC network in which multiple cardiovascular subcircuits interact (Figures 1 through 7). When the known components of this network are considered from the point of view of neuroimmune circuit physiology and pathophysiology, several points deserve attention: the interaction between arteries and the heart to form a CBC is only beginning to be understood as the 2 have largely been studied by relatively independent areas in the past.…”

“…194 Engrams are known to exceed the borders of a single brain nucleus by forming a collection of neurons stretching across several nuclei in a network-like pattern. 194 The identification of engrams in the CBC has not yet been accomplished directly but their existence is likely given the involvement of the immune system in forming engrams in other disease conditions and being involved in CVD progression: Thus, brain engrams have been shown to exist for physiological but also for pathophysiological responses involving the immune system [5][6][7][8]43,44,46,49,54,163,193,195 forming inflammation-related engrams that are defined as the ability of the brain to remember past tissue injury of any given peripheral organ. 6,163,196 Therefore, brain engrams can also be defined as regulatory units of neurons that store information about past physiological organ-to-brain connections or organ destruction.…”

“…Several recent lines of evidence point to a new—until recently elusive—circuit involving the arterial tree that we have termed the artery-brain circuit (ABC). 7,8,54 The ABC appears to interact with the much better-established heart-brain circuit (HBC) to form a large dynamic cardiovascular brain circuit (CBC). 26,27,35,55 In this review, we will discuss what is currently known about both the ABC and the HBC to form a global CBC network with its core constituents, that is, the arterial tree and the heart.…”

“…The human brain as the center of both interoception (perception from bodily signals) and exteroception (perception from the environment) is certainly the most complex tissue that nature has ever coined. 1–35 Indeed, if challenges can be overcome to make steps towards a better understanding of the brain, groundbreaking advances into human development and conceivably the pathogeneses of a large number of clinically important cardiovascular diseases (CVDs) may be within reach. 36 Defining control of physiological responses such as stress-related circuits have already uncovered aberrant interactions between the brain and peripheral organ dysfunction in diseases as diverse as cancer, 37 obesity, 24 metabolism and diabetes, 38 chronic lung diseases, 39,40 inflammatory bowel diseases, 20,41 autoimmune diseases, 42 psychiatric disorders, 43,44 and neural control of infectious diseases.…”