Designed angiopoietin-1 variant, COMP-angiopoietin-1, rescues erectile function through healthy cavernous angiogenesis in a hypercholesterolemic mouse

Scientific Reports
Ji-Kan RyuJun-Kyu Suh

Abstract

Despite the advent of oral phosphodiesterase-5 inhibitors, curative treatment for erectile dysfunction (ED) remains unavailable. Recently, the link between ED and cardiovascular disease was unveiled and the main etiology of ED was found to be vasculogenic. Therefore, neovascularization is a promising strategy for curing ED. Angiopoietin-1 (Ang1) is an angiogenic growth factor that promotes the generation of stable and functional vasculature. Here, we demonstrate that local delivery of the soluble, stable, and potent Ang1 variant, COMP-Ang1 gene or protein, into the penises of hypercholesterolemic mice increases cavernous angiogenesis, eNOS phosphorylation, and cGMP expression, resulting in full recovery of erectile function and cavernous blood flow up to 8 weeks after treatment. COMP-Ang1-induced promotion of cavernous angiogenesis and erectile function was abolished in Nos3(-/-) mice and in the presence of the NOS inhibitor, L-NAME. COMP-Ang1 also restored the integrity of endothelial cell-cell junction by down-regulating the expression of histone deacetylase 2 in the penis of hypercholesterolemic mice and in primary cultured mouse cavernous endothelial cells. These findings constitute a new paradigm toward curative treatment ...Continue Reading

References

Mar 21, 1998·The Journal of Clinical Investigation·R D RudicW C Sessa
May 15, 1998·The New England Journal of Medicine·I GoldsteinP A Wicker
Oct 17, 1998·Science·C SuriG D Yancopoulos
Mar 31, 2000·Nature Medicine·G ThurstonG D Yancopoulos
Jul 18, 2000·Journal of the American College of Cardiology·D J WebbW W Dinsmore
Sep 27, 2000·Circulation·T O Cheng
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·J K ChaeG Y Koh
Jan 24, 2002·European Urology·J M Martínez-JabaloyasF García-Sisamón
May 2, 2003·Current Hypertension Reports·Stefan John, Roland E Schmieder
May 22, 2003·The American Journal of Pathology·Saeid BabaeiDuncan J Stewart
Apr 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
Apr 20, 2004·Journal of the American College of Cardiology·Maple M FungElizabeth Barrett-Connor
Jun 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Trinity J BivalacquaPhilip J Kadowitz
Jan 25, 2005·International Journal of Urology : Official Journal of the Japanese Urological Association·Sing Joo ChiaArul Earnest
Mar 9, 2005·Drugs of Today·Muammer KendirciWayne J G Hellstrom
Jan 18, 2006·JAMA : the Journal of the American Medical Association·Ian M ThompsonCharles A Coltman
Feb 15, 2007·International Journal of Andrology·Shuguang PiaoJun-Kyu Suh
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Oct 20, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Courtney P JudkinsGrant R Drummond
Oct 28, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhifei WangDe-Maw Chuang

❮ Previous
Next ❯

Citations

Feb 19, 2016·International Journal of Impotence Research·J H KimY S Song
May 23, 2017·Nature Reviews. Drug Discovery·Pipsa SaharinenKari Alitalo
Aug 18, 2017·International Journal of Molecular Sciences·Deok-Hoon KongSukmook Lee

❮ Previous
Next ❯

Software Mentioned

SigmaStat

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.