TNF and inflammatory response: However, in patients with PAD, the underlying disease state is characterized by chronic inflammation, endothelial cell dysfunction, arterial remodeling, and increased vascular stiffness—a pathophysiological milieu that can blunt or outweigh the protective effects of thyroid hormone (32, 33)—for instance, PAD is associated with elevated levels of pro-inflammatory cytokines (e.g., IL-6, TNF-α) and endothelial adhesion molecules, reflecting ongoing vascular inflammation and damage that limit NO bioavailability and normal endothelial responsiveness.