In diseases such as hypertension, aging, atherosclerosis, diabetes and chronic kidney disease, arterial calcification and stiffening of the elastic layer of the arterial wall are almost always present.
Think of it like bones forming inside your arteries.
“Arterial calcification resembles osteogenesis, or bone formation, in which arterial smooth muscle cells (SMCs) within the arterial wall transform into osteoblast-like cells, or bone cells, that express many of the proteins associated with bone formation and release exosomes,” said Yang Zhang, associate professor of pharmacology at the UH College of Pharmacy.
Exosomes are very small particles that may carry various substances like lipids, RNAs or proteins. Zhang has received $2.5 million from the National Heart Lung and Blood Institute to explore a new mechanism involving genes that regulate exosome secretion, which may contribute to the development of arterial calcification.
“Exosomes are not simply bystanders, they are released and bind to the extracellular matrix (EM), and the exosome-EM niche serves as sites for the accumulation of crystals that are part of calcification,” said Zhang.
Before exosomes are released, they could be degraded by lysosomes, which are parts of a cell that contain degradative enzymes. Compromised lysosome function would enhance exosome secretion and thereby promote the development of arterial calcification.
“We observed that the deletion of a lysine methyltransferase gene in SMCs is associated with lysosome trafficking dysfunction, increased exosome release and enhanced osteogenic transformation in SMCs as well as accelerated arterial calcification,” said Zhang. In this project, he will determine the factors affected by lysine methylation that may modulate lysosome trafficking function.
“Our findings will help us understand how arterial hardening starts within cells at the very early stage of patients with cardiovascular risk factor such as hyperlipidemia and hyperphosphatemia,” said Zhang.
These findings may also identify therapeutic targets for the treatment and prevention of arterial hardening under different pathological conditions.