<p>A Systematic Review on Rho-Kinase as a Potential Therapeutic Target for the Treatment of Erectile Dysfunction</p>

Abstract

Background: Erectile dysfunction (ED) is a common clinical condition with limited treatment options. The main aim of the present systematic review was to synthesize information on Rho-kinase as a novel therapeutic approach for the treatment of ED. Methods: We performed a systematic literature study in PubMed, Google Scholar and Scopus. Included studies were original articles studied the role of Rho-kinase in the pathogenesis and/or new treatment approach for ED in animal models and clinical studies, published between 2014 and 2019. Data derived from each study were study design used, interventions applied and main treatment outcomes. The quality of the selected articles was assessed by CAMARADES criteria and data were analyzed using descriptive statistics. Results: A total of 1067 original articles were retrieved in the given period and eighteen papers met our inclusion criteria. Five articles explain the role of Rho-kinase in ED pathogenesis using different models such as cavernous nerve crush injury, heart failureinduced ED, vasculogenic and post-radical prostatectomy ED, diabetes-induced ED and agerelated ED. Other ten papers explain the role of novel drugs evaluated for ED treatment by targeting Rho-kinase as a new approach for ED therapy. The rest three papers discuss the role of plant extracts used by traditional society for the treatment of ED and assess their potential function in targeting Rho-kinase in animal models. The penile erectile functional index has shown that the ratio of intracavernosal pressure to mean arterial pressure (ICP/MAP) was decreased due to age and various chronic diseases. Whilst, ROCK I and ROCK II expression were increased. Western blot findings have also shown that ROCK II and MYPT-1 phosphorylation rates increased in cavernous tissue after ED induction. Besides, compounds which can inhibit the action of Rho-kinase activity showed relaxation of the corpus cavernosum, decrease in corporal fibrosis, and alleviate increased apoptosis and caspase-3 activity in an NO-independent manner. Moreover, histological and molecular dysregulation have been improved by inhibition of Rho-kinase. Conclusion: Targeting Rho-kinase may be a possible target for the treatment of ED secondary to specific causes, and Rho-kinase inhibitors may be a new drug family for the treatment of ED. However, this requires further studies for in-depth understanding.

Erectile dysfunction and diabetes: A melting pot of circumstances and treatments

“…To this regard, inhibition of RhoA-ROCK signalling seems to potentiate smooth muscle relaxation in an NO-independent manner and could be considered a new therapeutic target for the treatment of ED. [181][182][183] Considering angiotensin-II (Ang II), which is the primary effector of the RAS, studies have demonstrated the presence and activity in the penis. In fact, elevated Ang II levels contribute to the development of ED both in humans and animal models 184 and might be considered as a promising therapeutic target for the treatment of ED.…”

“…RhoA/ROCK signalling play a role in the maintaining of the flaccid penile state and its activity in the penis is a pathogenic factor contributing to ED development. To this regard, inhibition of RhoA‐ROCK signalling seems to potentiate smooth muscle relaxation in an NO‐independent manner and could be considered a new therapeutic target for the treatment of ED 181‐183 …”

“…To this regard, inhibition of RhoA‐ROCK signalling seems to potentiate smooth muscle relaxation in an NO‐independent manner and could be considered a new therapeutic target for the treatment of ED. 181 , 182 , 183 …”

A visualization system for erectile vascular dynamics

“…ROCK has two isoforms, ROCK 1 and ROCK 2, which are involved in physiological and pathological signaling pathways (Sopko et al, 2014). ROCK is a primary downstream factor activated through RhoA (Roser et al, 2017;Zewdie et al, 2020). In addition to its regulation of cytoskeletal dynamics, they induced contractile responses in vascular smooth muscle cells (Hirooka and Shimokawa, 2005;Schofield et al, 2012;Loirand, 2015;Zewdie et al, 2020).…”

“…ROCK is a primary downstream factor activated through RhoA (Roser et al, 2017;Zewdie et al, 2020). In addition to its regulation of cytoskeletal dynamics, they induced contractile responses in vascular smooth muscle cells (Hirooka and Shimokawa, 2005;Schofield et al, 2012;Loirand, 2015;Zewdie et al, 2020). The RhoA-ROCK activity inhibits eNOS and regulates the contractile state of the sinusoids (Chitaley et al, 2001;Chitaley et al, 2003;Sugimoto et al, 2007;Sopko et al, 2014).…”