Treatment of endothelial cell dysfunction in atherosclerosis: a new perspective integrating traditional and modern approaches

Atherosclerosis begins at the artery’s inner lining — the endothelium — and this wide-ranging review centers treatment there, spanning the well-established to the frankly experimental.

The unifying biology is nitric oxide: endothelial dysfunction is, at its core, a loss of NO availability driven by oxidative stress, and most therapies work by restoring that axis. The review’s useful insight is that familiar cardiovascular drugs — statins, blood-pressure agents, and newer diabetes drugs like SGLT2 inhibitors and GLP-1 agonists — protect the endothelium through “pleiotropic” effects beyond their main job, which strengthens the case for using them in high-risk patients. It also flags an important nuance on exercise: moderate intensity helps the endothelium, while acute high-intensity bouts may transiently harm it. The frontier — stem cells, gene therapy, nanomedicine, microRNA targets — is surveyed but candidly early.

The practical takeaway: endothelial dysfunction is a potentially reversible early stage, treatable today with lifestyle and drugs whose vascular benefits exceed their labels, with newer approaches still investigational.

We rate the evidence solid for a review: a 198-reference synthesis bridging mechanism and therapy, though weighted toward preclinical data for the novel approaches. Its clinical significance is moderate-to-high — the mechanistic rationale for existing drugs’ endothelial benefits is actionable now, while the emerging therapies remain a research horizon.