Coronary Artery Disease(CAD) arising from atherosclerosis and atherothrombotic events has been the leadingcause of death worldwide since the last few decades except in the very low-incomegroup population (WHO factsheet). Atherothrombosis and atherosclerosis are thepathologic basis for CAD and is widely appreciated to be a multifactorialdisease with predominant factors of elevated lipid levels and chronicinflammation (PMID: 20065951, 22064431). Emphasizing the role of lipids, statinshave been the gold standard for treating CAD and a large amount of randomizedcontrolled statin trials have confirmed the beneficial effects in variouspatient groups of CADs (PMID 26892969). However, it is only in the last threedecades that evidence from experimental and clinical studies has lent supportto the inflammatory hypothesis, in the pathogenesis of atherosclerotic diseasein conjunction with or beyond elevated lipid levels. The recent results ofCANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) have now providedan unequivocal support for the inflammatory hypothesis of atherosclerosis whereclinical evidence that controlling vascular inflammation independently of lipidlowering could lower the rates of recurrent cardiovascular events in a largePhase 3 trial (PMID: 28845751).
Inflammatory signals probably cause plaqueinstability which could result in plaque rupture, fissuring, or erosion leadingto a thrombotic response that causes myocardial infarction. Yet, pureanti-inflammatory drugs have never been used to treat patients with CAD. Elevated Leukocyte count has been correlatedwith cardiovascular disease since the 1920s (PMID 15542275). Although the association betweenleukocytosis and increased morbidity and mortality of ischemic vascular diseaseis robust (PMID 15662026, 21866299), it is not clear whether the association iscausal in nature. The myeloid compartment of the WBCs namely, monocytes (PMID 27932363),neutrophils (PMID 25781147, 15288155) and platelets (PMID 12483207) are the predominantplayers and have all been implicated in influencing CAD initiation or progressionand impair the regression of atheromatous plaques.
In this context it is notsurprising to note that aspirin by virtue of its inhibition to plateletaggregation by blocking thromboxane A2 formation, has been used for severaldecades as the gold-standard in secondary prevention of CAD (PMID 8298418).Here we review the common theme of Myelopoiesis and specificallyMegakaryopoiesis, being the culprit in the pathogenesis of CAD with emphasis onreticulated platelets and the role of liver in regulating megakaryopoiesis andthrombopoiesis.
