Biomarkers of endothelial damage in erectile dysfunction based on preclinical studies: a systematic review.

PURPOSE: To determine the relationship between biomarkers and endothelial damage in animal models of experimentally induced erectile dysfunction. The biomarkers with the most robust evidence could be tested in future in human patients to assess their clinical significance in the diagnosis and follow-up of ED patients.

METHODS

This systematic review was conducted according to the recommendations of the Cochrane Collaboration and following the PRISMA Statement. We designed a search strategy in MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to the present. We assessed the risk of bias based on the SYRCLE tool for preclinical trials.

RESULTS

1208 animals were included in 34 studies. A total of 12 biomarkers were reviewed. Six markers showed decreased expression: eNOS in 18 studies (p < 0.05), in 9 studies (p < 0.01), and one study (p > 0.05); VEGF in 5 studies (p < 0.05) and one study (p < 0.01); nNOS in 1 study (p < 0.01) and in 1 study (p < 0.05); aSMA in 2 studies (p < 0.05); LncRNA in 1 study (p < 0.05); Hebp1 in 1 study (p < 0.001). Six markers showed increased expression: FACL-4, PACS-2, and IP3R1 in 1 study (p < 0.01, respectively); endocan in 1 study (p < 0.05); endothelial microparticles and endothelial progenitor cells in 1 study (p < 0.05, respectively). The six markers with decreased expression showed more than a 50% reduction compared to the control group. The six markers that showed increased expression demonstrated an increase of more than 50% compared to their respective comparison group. Selection, performance, and detection biases were identified in 100% of the studies.

CONCLUSION

eNOS; VEGF; nNOS; aSMA; LncRNA; and Hebp1 showed decreased expression in the presence of endothelial damage, while FACL-4; PACS-2; IP3R1; endocan; endothelial microparticles; and endothelial progenitor cells showed an increase under the same conditions. These could become markers with implications for clinical trials and the development of new targeted treatments for ED.