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Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction.

Abstract
Erectile dysfunction (ED) is a common and debilitating condition with high impact on quality of life. An underlying cause of ED is apoptosis of penile smooth muscle, which occurs with cavernous nerve injury, in prostatectomy, diabetic and aging patients. We are developing peptide amphiphile (PA) nanofiber hydrogels as an in vivo delivery vehicle for Sonic hedgehog protein to the penis and cavernous nerve to prevent the apoptotic response. We examine two important aspects required for clinical application of the biomaterials: if SHH PA suppresses intrinsic (caspase 9) and extrinsic (caspase 8) apoptotic mechanisms, and if suppressing one apoptotic mechanism forces apoptosis to occur via a different mechanism. We show that SHH PA suppresses both caspase 9 and 8 apoptotic mechanisms, and suppressing caspase 9 did not shift signaling to caspase 8. SHH PA has significant clinical potential as a preventative ED therapy, by management of intrinsic and extrinsic apoptotic mechanisms.
AuthorsSarah Martin, Daniel A Harrington, Samuel Ohlander, Samuel I Stupp, Kevin T McVary, Carol A Podlasek
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 37 Pg. 102444 (10 2021) ISSN: 1549-9642 [Electronic] United States
PMID34314869 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightPublished by Elsevier Inc.
Chemical References
  • Hedgehog Proteins
  • Hydrogels
  • Peptides
  • SHH protein, human
  • Caspase 8
  • Caspase 9
Topics
  • Animals
  • Apoptosis (drug effects)
  • Caspase 8 (genetics)
  • Caspase 9 (genetics)
  • Cavernous Sinus (drug effects, pathology)
  • Disease Models, Animal
  • Erectile Dysfunction (drug therapy, genetics, pathology)
  • Hedgehog Proteins (chemistry, genetics, pharmacology)
  • Humans
  • Hydrogels (chemistry, pharmacology)
  • Male
  • Nanofibers (chemistry)
  • Penis (drug effects, pathology)
  • Peptides (chemistry, pharmacology)
  • Prostatectomy (adverse effects)
  • Rats
  • Rats, Sprague-Dawley

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