VASCULAR EXPRESSION OF POLYCYSTIN

Autosomal dominant polycystic kidney disease (ADPKD) is predominantly caused by mutations of the gene PKD1, which encodes a large protein, p olycystin, of unknown function. A variety of arterial abnormalities oc cur with increased prevalence in ADPKD patients. Using an antiserum ag ainst the nonduplicated region of the polycystin protein, immunostaini ng of vascular smooth muscle cells was detected in normal adult elasti c arteries. Partial digestion of tissue slices with nonspecific protea ses greatly enhanced this staining. Similar enhancement was seen with specific elastase digestion. Immunostaining for smooth muscle actin wa s not affected by elastase. Antiserum preadsorbed with peptide antigen gave no staining. In specimens of intracranial aneurysms, aortic diss ections, and dolichoectatic arteries from thirteen patients with ADPKD , immunostaining of variable intensity for polycystin was demonstrated in arterial smooth muscle cells and myofibroblasts, along with disrup tion of elastic laminae. Further elastase digestion did not significan tly alter staining patterns. Intracranial aneurysms from patients with out ADPKD also showed a variable degree of immunostaining with polycys tin antisera in the same distribution. The expression of polycystin in arterial smooth muscle suggests a direct pathogenic role for ADPKD-re lated mutations in the arterial complications of this disease.