Aggravation of atherosclerosis by parathyroid hormone access

Abstract

Parathyroid hormone (PTH), primarily known for its role in calcium and phosphate metabolism, has increasingly been implicated in the development and progression of atherosclerosis. Elevated PTH levels, whether due to primary or secondary hyperparathyroidism, are linked to a higher risk of cardiovascular disease, including both subclinical and overt atherosclerotic vascular disease. Evidence shows that, PTH impairs endothelial function by increasing the production of reactive oxygen species (ROS), particularly mitochondrial ROS, which leads to oxidative stress and impaired vascular relaxation. This dysfunction is a key early event in atherogenesis. Moreover, PTH stimulates endothelial cells to upregulate the expression of inflammatory markers such as interleukin-6 (IL-6) and the receptor for advanced glycation end products (RAGE), both of which are involved in vascular inflammation and plaque formation. These effects are mediated via protein kinase A (PKA) and protein kinase C (PKC) pathways and are nitric oxide (NO) dependent. Chronic elevation of PTH also promotes apoptosis of vascular smooth muscle cells (VSMCs), which precedes and contributes to vascular calcification as a hallmark of advanced atherosclerosis, since PTH-induced calcification is associated with endoplasmic reticulum (ER) stress in VSMCs. Additionally, chronic hypercalcemia driven by high PTH levels accelerates calcification of vessel walls and atherosclerotic plaques. Finally, Elevated PTH is associated with metabolic disturbances such as hyperlipidemia and impaired glucose tolerance, both of which exacerbate the atherosclerotic process.

Keywords: Parathyroid hormone, Atherosclerosis, Parathormone, Endothelial cell, Nitric oxide, Reactive oxygen species