Abstract
Simple SummaryThe presented manuscript contains the most current and extensive summary of the role of the most predominant gastrointestinal hormones—GIP and GLP-1 in the pathophysiology of atherosclerosis and coronary artery disease both in animals and humans. We have described GIP and GLP-1 as (1) expressed in many human tissues, (2) emphasized relationship between GIP and GLP-1 and inflammation, (3) highlighted importance of GIP and GLP-1-dependent pathways in atherosclerosis and coronary artery disease and (4) proved that GIP and GLP-1 could be used as markers of incidence, clinical course and recurrence of coronary artery disease, and related to extent and severity of atherosclerosis and myocardial ischemia. Our initial review may state a cornerstone for the future, however, there are still many unknowns and understatements on this topic. Due to the widespread growing interest for the potential use of incretins in cardiovascular diseases, we think that further research in this direction is desirable. For the future, we would like to recognize GIP and GLP-1 as widely implemented into clinical practice as new biomarkers of atherosclerosis and coronary artery disease. Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications.
Highlights
Acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) are a group of clinical diagnosis related to myocardial ischemia and are both the manifestation of atherosclerosis in coronary arteries, named coronary artery disease (CAD)
In the very first research directly regarding this topic, Bose et al [72] investigated the effects of glucagon-like peptide-1 (GLP-1) infusion in vitro in rats subjected to 30 min of left main (LM) artery occlusion and 2 h of reperfusion and observed that GLP-1 had no salutary effects on hemodynamics
Four-week infusion of glucose-dependent insulinotropic polypeptide (GIP) significantly suppressed macrophage-driven atherosclerotic lesions and foam cell formation, but this effect was abolished by co-infusions with a GIP receptor (GIPR) antagonist
Summary
Acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) are a group of clinical diagnosis related to myocardial ischemia and are both the manifestation of atherosclerosis in coronary arteries, named coronary artery disease (CAD). Atherosclerosis is mainly a sequence of dyslipidemia that induces vascular cell dysfunction and causes inflammation, while the inflammatory process itself (without the accompanying dyslipidemia) may generate atherosclerotic plaque formation [2] Both lipid disorders as well as inflammation and pro-inflammatory molecules are potential therapeutic targets in atherosclerosis [2]. Often radiating to the left shoulder or angle of the jaw, sweating, nausea and vomiting, and shortness of breath are the first signs of acute occlusion of the culprit artery [4] If such a condition, named MI, happens, the pain in the chest usually lasts more than 20 min and increases and does not disappear at rest or after taking nitrates. Despite many clinical studies dedicated to it and an enormous development of diagnostic and therapeutic methods, new markers are still being sought to identify CAD and objectively for the implementation of optimal management as soon as possible
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
