To determine specific molecular features of endothelial cells (ECs) relevant to the physiological process of penile erection we compared gene expression of human EC derived from corpus cavernosum of men with and without erectile dysfunction (HCCEC) to coronary artery (HCAEC) and umbilical vein (HUVEC) using Affymetrix GeneChip microarrays and GeneSifter software. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. A total of 190 genes/transcripts were highly expressed only in HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix, pattern specification and organogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed high expression of genes relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, claudin 11 (CLDN11), desmoplakin, and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Overall, cavernosal ECs exhibited a transcriptional profile encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. Contribution of the tight junction protein CLDN11 to barrier function in endothelial cells is novel and may reflect hemodynamic requirements of the corpus cavernosum.

The corpus cavernosum is a specialized vascular organ in which endothelial cells (ECs) are exposed to a wide range of pressures (10–500 mmHg) during flaccidity and rigidity. The tight junction associated gene, claudin 11, is highly expressed in human cavernosal ECs (HCCECs) as compared to ECs from other blood vessels. We tested the hypothesis that claudin 11 plays an important role in barrier function in HCCECs by measuring transendothelial electrical resistance (TEER) following claudin 11 knock down. Ambion siRNA constructs for CLDN11 and a negative control scrambled sequence (SCR) were transfected into HCCECs using DharmaFECT‐1 (Dharmacon). Significant down‐regulation of claudin 11 was verified by Western blot at 2 and 7 days following transfection. Untransfected control (CNT), SCR siRNA, and CLDN11 siRNA transfected ECs were seeded in 6.5‐mm Transwell inserts and integrity of the endothelial monolayer assessed by daily measurements of TEER with an Endohm‐6 electrode chamber and an EVOM voltohmmeter (World Precision Instrument). HCCECs transfected with CLDN11 siRNA had significantly reduced TEER compared to both SCR and CNT groups (% of CNT at 75.5 and 95hr: 73±8.7 and 76±8.9, p<0.05). There was no significant difference in TEER in the SCR siRNA vs. CNT group (% of CNT at 75.5 and 95hr: 97.1±2.2 and 98.5±1.9). These data suggest that claudin 11 is important for cavernosal EC junctions and barrier function.