ECSOD

ECSOD stands for extracellular superoxide dismutase, an enzyme in the copper- and zinc-dependent family that dismutates superoxide radicals in the extracellular space. In humans it is encoded by the SOD3 gene and is typically referred to as EC-SOD or SOD3. The mature enzyme is secreted and mainly functions as a tetramer, with each subunit containing the cofactors copper and zinc required for catalysis.

A distinctive feature of EC-SOD is its amino-terminal heparin-binding domain, which anchors the enzyme to extracellular matrix components such as heparan sulfate proteoglycans and collagen. This localization concentrates antioxidant activity in vascular and connective tissue matrices and in lung extracellular fluid, helping to limit oxidative damage beyond the cell surface.

Physiologically, EC-SOD is highly expressed in the lungs and vascular tissues and is produced by fibroblasts, smooth muscle cells, and macrophages, among others. Its activity protects nitric oxide signaling by reducing extracellular superoxide, thereby supporting vasodilation and vascular function. Regulation of SOD3 expression can be influenced by cytokines, oxidative stress, and hypoxic conditions.

Clinical relevance is explored in the context of oxidative stress-related diseases. Altered EC-SOD activity or levels have been reported in hypertension, atherosclerosis, chronic obstructive pulmonary disease, and ischemia–reperfusion injury. A common genetic variant, Arg213Gly in the SOD3 gene, affects the enzyme’s binding to the extracellular matrix and has been associated with various cardiovascular and pulmonary conditions in some studies, though findings are not universally conclusive.

Research continues on EC-SOD as a potential therapeutic antioxidant, including approaches to increase extracellular enzyme levels or activity.