Vascular expression of polycystin

Autosomal dominant polycystic kidney disease (ADPKD) is predominantly caused by mutations of the gene PKD1, which encodes a large protein, polycystin, of unknown function. A variety of arterial abnormalities occur with increased prevalence in ADPKD patients. Using an antiserum against the nonduplicated region of the polycystin protein, immunostaining of vascular smooth muscle cells was detected in normal adult elastic arteries. Partial digestion of tissue slices with nonspecific proteases greatly enhanced this staining. Similar enhancement was seen with specific elastase digestion. Immunostaining for smooth muscle actin was not affected by elastase. Antiserum preadsorbed with peptide antigen gave no staining. In specimens of intracranial aneurysms, aortic dissections, 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 disruption of elastic laminae. Further elastase digestion did not significantly alter staining patterns. Intracranial aneurysms from patients without ADPKD also showed a variable degree of immunostaining with polycystin antisera in the same distribution. The expression of polycystin in arterial smooth muscle suggests a direct pathogenic role for ADPKD-related mutations in the arterial complications of this disease.