E-Cigarette-Associated Endothelial Damage: A Potential Mechanism for Erectile Dysfunction

Pincus, Joshua; Sandoval, Víctor; Dick, Brian; Sanekommu, Ganesh; Rajasekaran, Raj; Ramasamy, Ranjith; Raheem, Omer

doi:10.1016/j.sxmr.2021.01.003

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…Dysfunction of intestinal endothelial cells leads to intestinal in ammation, and dysfunction of cavernous endothelial cells leads to poor erectile function. Endothelial cell dysfunction is regarded as a important cause of a variety of pathologic Settings such as cardiovascular disease, erectile dysfunction, and intestinal injury [23,24]. The correlation between IBD and ED found in some clinical studies also seemed to indicate that the two diseases are related at the genetic and molecular level, which prompts us to look for genetic answers from the GEO database.…”

Section: Discussionmentioning

confidence: 99%

Potential common molecular mechanisms between inflammatory bowel disease and erectile dysfunction in men: genetic screening and in vivo validation

Wang,

Xiao,

Pan

2024

Preprint

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Purpose: To explore Potential common molecular mechanisms between inflammatory bowel disease and erectile dysfunction in men. Method: First, differentially expressed genes in GSE10804 dataset and GSE191234 dataset were identified. qRT-PCR to verify the expression of differential genes. Enrichment analysis was performed in GO, KEGG and PPI. Result: From public GEO datasets of IBD and ED, we mined 15 genes that work together on both diseases and validated them in mice with inflammatory bowel disease, finding the importance of several genes. Among them, the common KEGG pathway of the DEGs in the two datasets includes calcium signaling pathway and cell adhesion molecules, cytoskeleton in muscle cells, protein digestion and absorption, and tyrosine metabolism. In vivo, ABAC8, ADGRF5, CLGN, GRM1, NUAK1, PDE1A, SLC39A8 were verified by statistical difference. Conclusion: Potential common genes interaction between inflammatory bowel disease and erectile dysfunction may be related to ABAC8, ADGRF5, CLGN, GRM1, NUAK1, PDE1A, SLC39A. calcium signaling pathway and cell adhesion molecules, cytoskeleton in muscle cells, protein digestion and absorption, and tyrosine metabolism may be the potential mechanism.

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Section: Discussionmentioning

confidence: 99%

Potential common molecular mechanisms between inflammatory bowel disease and erectile dysfunction in men: genetic screening and in vivo validation

Wang,

Xiao,

Pan

2024

Preprint

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“…Endothelial cell dysfunction, injury, and death remain the leading causes of diverse pathological settings such as cardiovascular diseases, erectile dysfunction, and ischemia–reperfusion injuries. 12-14 A growing number of published studies in this field suggest that the accumulation of lipids can pose a threat to the normal function of ECs. 15 , 16 Proinflammatory molecules can be generated in ECs by saturated FFAs such as myristic acid (C14:0), PA (C16:0), and stearic acid (C18:0), which may be mediated through the alteration of cell membrane properties to activate Toll-like receptors.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis highlights the role of ferroptosis in palmitic acid–induced endothelial dysfunction

Tan

Nan

et al. 2023

Sexual Medicine

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Background Palmitic acid (PA) has a lipotoxic effect on blood vessels, leading to endothelial dysfunction and cell death. The underlying mechanisms are not yet fully understood. Aim We sought to investigate the effects of PA on endothelial cells, with an emphasis on ferroptosis. Methods Rat corpus cavernosum endothelial cells (RCCECs) and human umbilical vein endothelial cells (HUVECs) were treated with PA to induce a pattern of cell death, as evidenced by the evaluation of cell viability. The differentially expressed genes were measured via RNA sequencing to reveal potential mechanisms. The intracellular levels of glutathione (GSH), malondialdehyde (MDA), ferrous ion (Fe2+), and reactive oxygen species (ROS) were evaluated using commercial kits. Western blot was performed to determine the expressions of relative proteins. Outcomes At the end of the study period, the evaluated outcomes were cell viability, transcriptome profiles, the expressions of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11), as well as levels of GSH, MDA, Fe2+, and ROS. Results PA-induced cell death of RCCECs and HUVECs was demonstrated in a dose- and time-dependent manner. Based on the findings of RNA-sequencing (RNA-seq), enrichment of many biological processes associated with cell cycle and response to stimulus occurred. More importantly, ferroptosis was highlighted in the bioinformatic analysis of both endothelial cells. The levels of intracellular Fe2+, MDA, and ROS were significantly increased following PA exposure while GSH was decreased, suggesting excessive iron accumulation, development of lipid peroxidation, and imbalanced redox homeostasis. Mechanistically, PA decreased the protein expression levels of GPX4 and SLC7A11 in endothelial cells, both of which played crucial roles in ferroptotic cell death. Clinical Translation This study suggests that ferroptosis may be a useful target for novel therapeutic interventions for endothelial dysfunction and cell death in vascular diseases such as erectile dysfunction. Strengths and Limitations In this study, we found that ferroptosis could participate in PA-induced endothelial dysfunction and cell death. A limitation of the study is that it did not shed light on the overall mechanisms of this process. Therefore, further research on the intricate networks of regulating ferroptosis is needed. Conclusion Overall, the occurrence of ferroptosis was demonstrated in the PA-treated HUVECs and RCCECs in this study.

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“…For example, urologists can define stuttering priapism and highlight that it was found to be associated with e-cig use [4]. Following this, it is worthwhile discussing that e-cig use is associated with lower sperm count [6], lower sperm concentration [7], lower sperm movement [7], and erectile dysfunction [8]. It is necessary to acknowledge that the longterm impacts of e-cig use on sexual health are still unknown, therefore, it is possible that e-cig use can impact sexual development in the present and fertility over the life course.…”

Section: Screening Questions Question Rationalementioning

confidence: 99%

“…Recent research highlights that e-cig use may have a negative impact on sexual health, namely, that e-cigs can have a negative impact on the genitourinary system [4][5][6][7][8][9]. Alzahrani et al [4] found that e-cig use was associated with stuttering priapism, which are episodes that involve repetitive prolonged erections.…”

Section: Introductionmentioning

confidence: 99%

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Discussing the Sexual Health Impacts of Electronic Cigarette Use with Youth: A Proposed Framework to Support Urologists

Bandara,

Lalkiya,

Alhamam

et al. 2023

Future

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The sexual health of young people during the youth age period is of utmost importance, as it sets the stage for sexual well-being over the life course. In addition to the existing challenges that youth face concerning their sexual health, electronic cigarettes may also negatively impact their sexual well-being. Specifically, through issues such as stuttering priapism, reduced sperm quality and quantity, and erectile dysfunction. Electronic cigarette use among youth is prevalent. Therefore, given the negative sexual health impacts associated with electronic cigarette use, coupled with the prevalent use of electronic cigarettes, it is necessary for youth to receive adequate support and guidance, so they understand the potential impacts that electronic cigarette use can have on their sexual well-being. Urologists are uniquely situated to play an important role in supporting the sexual health of youth, given their medical and surgical knowledge, however, it appears that they do not receive adequate training to carry out discussions about sexual health with youth. This paper aims to support urologists to have discussions with youth patients on the impact that electronic cigarettes have on their sexual health through a proposed four-step framework. This four-step framework involves: (i) establishing the relationship, (ii) assessing current electronic cigarette use, (iii) sharing research examining the impact of electronic cigarettes on sexual health, and (iv) discussing strategies to prevent/reduce or stop electronic cigarette use. It is necessary to acknowledge that this framework is only a small component of efforts to educate youth on the impacts that electronic cigarettes have on their sexual health. Moving forward, implementation and evaluation of this framework is needed.

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E-Cigarette-Associated Endothelial Damage: A Potential Mechanism for Erectile Dysfunction

Cited by 8 publications

References 32 publications

Potential common molecular mechanisms between inflammatory bowel disease and erectile dysfunction in men: genetic screening and in vivo validation

Potential common molecular mechanisms between inflammatory bowel disease and erectile dysfunction in men: genetic screening and in vivo validation

Transcriptome analysis highlights the role of ferroptosis in palmitic acid–induced endothelial dysfunction

Discussing the Sexual Health Impacts of Electronic Cigarette Use with Youth: A Proposed Framework to Support Urologists

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