Exosome Signaling in Vascular Calcification
Calcification of soft tissues occurs in the cardiovascular system with age, one of the processes that causes arterial stiffening and other pathogenic conditions such as aortic stenosis. Considered at a very high level, this happens because a fraction of cells in the blood vessel walls malfunction and begin to act in ways more appropriate to a bone environment, laying down deposits of minerals. The causes of this malfunction are incompletely understood, but evidence suggests that the presence of senescent cells and their inflammatory signaling is an important cause.
In this open access paper, researchers investigate cellular signals carried via exosomes in the context of vascular calcification. Exosomes are a class of extracellular vesicle, small membrane-bound packages of molecules that carry a sizable fraction of the signaling traffic between cells. In recent years, scientists have been paying a lot more attention to these packages, as they appear to carry most of the signals that are important in, for example, the beneficial effects of stem cell transplants. They are also probably a sizable part of the harmful signals produced by senescent cells. While the authors don't mention cellular senescence here, it is interesting to speculate on the overlap between this research and what is being discovered of the role of vesicles in senescent signaling.
Vascular calcification (VC) is caused by hydroxyapatite deposition in the intimal and medial layers of the vascular wall, leading to severe cardiovascular events in patients. Importantly, exosomes have been demonstrated to be involved in VC recently. Exosomes have up-regulated secretion from vascular smooth muscle cells (VSMCs) in vivo after pro-calcifying stimulation and become "calcifying" exosomes to induce VC. Calcium binds with phosphate to form hydroxyapatite nodes on the inner and outside of "calcifying" exosomes membranes, which further initializes mineral deposition. Although these studies did reveal that exosomes participated in the calcification procession through promoting mineral deposition sites formation, they did not discuss exosomes functioning as mediators for RNAs transportation, which is vital for exosome function.
Exosomes are secreted by diverse cells to mediate cell-to-cell communications. However, how exosomes regulate VC has been only preliminarily explored. It is found that exosomes with diverse origins mainly mediate microRNAs (miRs) transporting to VSMCs in coronary artery calcification. A bioinformatics analysis revealed that cultured in osteogenic medium, mesenchymal stem cells secreted exosomes with alterations of miRs, comparing with normal culturing. Such alterations were suggested to accelerate calcification in other mesenchymal stem cells to modulate osteogenic phenotype transition. Thus, it implies that besides heterogeneous mineral deposition inside vessel wall, exosomes can also promote VC by transporting messages among cells.
A lot of artery calcification is probably under genetic control and is dependent on what gene SNP's and alleles you inherited. The VKORCI gene SNP's rs9934438 and rs2359612 are known to keep Vitamin K and suppress calcification of arteries if you are homozygous for the G allele, which I have in duplicate. Another gene with longevity benefits that reduces calcification is EPHX2 rs7844965, again it is the G allele that reduces arterial calcification (Pilling, Dec., 2017, Human Longevity: 25 genetic loci associated with 39K UK Biobank Participants) and I have the GG allele combo. I had my arteries scanned about 2 years ago and no calcium plaques were found, and I am 77 years old.
PS: Please insert the word active after Vitamin K in the above comment. Another genetic factor that reduces artery calcium plaque from forming is Humanin, a peptide produced by a mitochondria gene MT RNR2 SNP rs2854128 A allele. Humanin is released into the blood stream and protects the blood vessel endothelium from atherosclerosis and calcium plaque formation if you have the A allele. It is another reason why you want to keep your mitochondria in tip top condition as you age, so that you get maximum amounts of humanin in your blood stream.