Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients

Abstract

Microbial communities are considered decisive for maintaining a healthy situation or for determining diseases. Acute myocardial infarction (AMI) is an important complication of atherosclerosis caused by the rupture of atheroma plaques containing proinflammatory cytokines, reactive oxygen species, oxidized low-density lipoproteins (oxLDL), damaged proteins, lipids, and DNA, a microenvironment compatible with a pathogenic microbial community. Previously, we found that archaeal DNA-positive infectious microvesicles (iMVs) were detected in vulnerable plaques and in the sera of Chagas disease patients with heart failure. Now, we characterize and quantify the levels of serum microbiome extracellular vesicles through their size and content using morphomolecular techniques to differentiate clinical outcomes in coronary artery disease (CAD). We detected increased numbers of large iMVs (0.8–1.34 nm) with highly negative surface charge that were positive for archaeal DNA, Mycoplasma pneumoniae antigens and MMP9 in the sera of severe AMI patients, strongly favoring our hypothesis that pathogenic archaea may play a role in the worst outcomes of atherosclerosis. The highest numbers of EVs <100 nm (exosomes) and MVs from 100 to 200 nm in the stable atherosclerotic and control healthy groups compared with the AMI groups were indicative that these EVs are protective, entrapping and degrading infectious antigens and active MMP9 and protect against the development of plaque rupture.Conclusion: A microbiome with pathogenic archaea is associated with high numbers of serum iMVs in AMI with the worst prognosis. This pioneering work demonstrates that the morphomolecular characterization and quantification of iEVs in serum may constitute a promising serum prognostic biomarker in CAD.

Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

“…A pioneering study by Moreno et al, found that the composition of the microbiome in patients with coronary artery disease may dictate clinical outcomes after cardiovascular events [180]. These microbial communities may release EVs during the onset of myocardial injury, which, depending on their origin, could be enriched in MMP9 and elicit a protective role during plaque rupture [180].…”

“…A pioneering study by Moreno et al, found that the composition of the microbiome in patients with coronary artery disease may dictate clinical outcomes after cardiovascular events [180]. These microbial communities may release EVs during the onset of myocardial injury, which, depending on their origin, could be enriched in MMP9 and elicit a protective role during plaque rupture [180]. Likewise, Ni et al characterized the protein profile of serum exosomes from atrial fibrillation patients and found 40 elevated proteins and 75 reduced proteins when compared to healthy controls [181].…”

Detecting early‐warning biomarkers associated with heart‐exosome genetic‐signature for acute myocardial infarction: A source‐tracking study of exosome

“…This has been shown to indicate pathophysiology or physiological changes and has emerged as a non‐invasive liquid biopsy strategy for cardiovascular diseases 4 . Altered micro ribonucleic acid (RNA) and messenger RNA (mRNA) in plasma total exosomes from various tissues have proven to be useful for assessing the extent of disease among different stages of CAD and play an essential role in biological processes from SCAD to AMI 2,5,6 . However, plasma total exosomes are heterogeneous vesicles comprising multiple sub‐populations secreted by various tissues, and the genetic networks between these sub‐populations and different organs are complex 7 .…”

“… 4 Altered micro ribonucleic acid (RNA) and messenger RNA (mRNA) in plasma total exosomes from various tissues have proven to be useful for assessing the extent of disease among different stages of CAD and play an essential role in biological processes from SCAD to AMI. 2 , 5 , 6 However, plasma total exosomes are heterogeneous vesicles comprising multiple sub‐populations secreted by various tissues, and the genetic networks between these sub‐populations and different organs are complex. 7 Only analysing the genetic information of plasma total exosomes is likely to be complicated by exosomes derived from other organs except for the heart.…”