Pathophysiology and mechanisms of Acute Coronary Syndromes: atherothrombosis, immune-inflammation, and beyond

ABSTRACT

Introduction

The pathophysiology of atherosclerosis and its acute complications, such as the Acute Coronary Syndromes (ACS), is continuously under investigation. Immunity and inflammation seem to play a pivotal role in promoting formation and grow of atherosclerotic plaques. At the same time, plaque rupture followed by both platelets’ activation and coagulation cascade induction lead to intracoronary thrombus formation. Although these phenomena might be considered responsible of about 90% of ACS, in up to 5–10% of acute syndromes, a non-obstructive coronary artery disease (MINOCA) might be documented. This paper gives an overview on atherothrombosis and immuno-inflammation processes involved in ACS pathophysiology, also emphasizing the pathological mechanisms potentially involved in MINOCA.

Areas covered

The relationship between immuno-inflammation and atherothrombosis is continuously updated by recent findings. At the same time, pathophysiology of MINOCA still remains a partially unexplored field, stimulating the research of potential links between these two aspects of ACS pathophysiology.

Expert opinion

Pathophysiology of ACS has been extensively investigated; however, several gray areas still remain. MINOCA represents one of these areas. At the same time, many aspects of immune-inflammation processes are still unknown. Thus, research should be continued to shed a brighter light on both these sides of “ACS” moon.

KEYWORDS:

• Atherosclerosis
• Immune-inflammation
• MINOCA
• thrombosis

Article highlights

• Atherothrombosis plays a key role in the majority of ACS: plaque rupture exposes intraplaque thrombogenic components to the flowing blood, such as TF, leading to coagulation cascade activation with final intravascular thrombus formation.

• The immuno-inflammatory modulation of atherosclerosis with still unknown “intraplaque antigen” activation of the immunocompetent cells is now well documented and accepted.

• Platelet aggregation cannot be considered only the final event of coagulation cascade. Activation of platelets occurs via a complex process that involves modulation of the proteome, transcriptome, and miRNOme.

• A not negligible percentage of ACS is related to non-obstructive CADs (MINOCA) where a macrovascular or microvascular disorder may occur.

• Several gray areas remain to be explored: 1) the identification of possible antigens responsible of activation of immuno-inflammation cells; 2) the definition of platelet role beyond thrombosis; and 3) the improvement of our knowledge on the pathophysiology of MINOCA to provide the patients with the best tailored therapy.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.

Additional information

Funding

This paper funded by V:ALERE 2019 grant from University of Campania Luigi Vanvitelli.