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Cytomegalovirus (CMV) is a member of the β-herpesviruses and is ubiquitous, infecting 50%-99% of the human population depending on ethnic and socioeconomic conditions. CMV establishes lifelong, latent infections in their host. Spontaneous reactivation of CMV is usually asymptomatic, but reactivation events in immunocompromised or immunosuppressed individuals can lead to severe morbidity and mortality. Moreover, herpesvirus infections have been associated with several cardiovascular and post-transplant diseases (stroke, atherosclerosis, post-transplant vasculopathy, and hypertension). Herpesviruses, including CMV, encode viral G-protein-coupled receptors (vGPCRs) that alter the host cell by hijacking signaling pathways that play important roles in the viral life cycle and these cardiovascular diseases. In this brief review, we discuss the pharmacology and signaling properties of these vGPCRs, and their contribution to hypertension. Overall, these vGPCRs can be considered attractive targets moving forward in the development of novel hypertensive therapies., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Erectile dysfunction (ED) has been shown to be related with inflammatory markers in humans. Chronic infusion of TNF-α caused ED in mice while TNF-α knockout mice exhibited improvement in the relaxation of the corpus cavernosum (CC)., Aim: Since obesity triggers an inflammatory process, we aimed to investigate the hypothesis that in obesity, Toll-like receptor 9 (TLR9) activation leads to increased TNF-α levels and impairment in CC reactivity., Methods: Four-week old male C57BL6 (WT) and TLR9 mutant (TLR9 MUT ) mice were fed a standard chow or high fat diet (HFD) for 12 weeks. Body weight and nonfasting blood glucose were analyzed. Contractile and relaxation responses of the CC were evaluated by electrical field stimulation and concentration response curves to phenylephrine and acetylcholine. Protein expression of nNOS, TNF-α, TNF-R1, TLR9 and MyD88 were measured by western blot. Plasma levels of TNF-α were measured by ELISA., Outcome: In obesity, impaired cavernosal relaxation is associated with the activation of the innate immune system, by increasing the production of TNF-α through the activation of TLR9 in the macrophages., Results: After 12 weeks of HFD both WT and TLR9 MUT mice had increased body weight and nonfasting blood glucose compared to standard chow. In the CC, acetylcholine-induced relaxation was not changed. A trend to increased contraction to phenylephrine and KCl was seen in WT HFD only. electrical field stimulation-induced relaxation of the CC was decreased in WT HFD as well as nNOS expression in the CC of WT HFD, but not in TLR9 MUT HFD. In the CC, protein expression of TLR9 and MyD88 was similar in all groups. While circulating levels of TNF-α presented only a trend to increase in mice fed HFD, the CC expression of TNF-α was increased only in WT HFD mice., Clinical Translation: The innate immune system can be a target for the treatment of erectile complications in obesity., Strengths and Limitations: This is the first study demonstrating that activation of TLR9 expressed in macrophages leads to impaired cavernosal relaxation. The main limitation of the study is the lack of understanding about the source/expression of the macrophages in the cavernous tissue. Further, herein, the experiments were performed only in isolated cavernous tissue (in vitro), thus the lack of knowledge on how the TLR9 modulates the in vivo response of the erectile tissue is another limitation of this study., Conclusion: Our findings indicate that CC dysfunction observed in obesity is at least in part mediated by the production of TNF-α upon activation of TLR9 expressed in the macrophages. Priviero F, Calmasini F, Dela Justina V, et al. Macrophage-Specific Toll Like Receptor 9 (TLR9) Causes Corpus Cavernosum Dysfunction in Mice Fed a High Fat Diet. J Sex Med 2021;18:723-731., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Male and female sexual dysfunction (SD) is considered a multifactorial condition. Numerous studies have shown the involvement of inflammatory processes in this pathological condition. Sexual intercourse requires healthy and functioning vessels to supply the pelvic region in both males and females, generating penile erection and clitoral and vaginal lubrication, respectively. Cardiovascular diseases and associated risk factors may contribute negatively to pelvic blood flow, possibly through immune system activation., Aim: The study aimed to address the correlation between vascular inflammation driven by immune system activation and SD in males and females., Methods: A literature review was performed to identify articles addressing male and female SD and vascular inflammation. Key words included "male and female sexual dysfunction," "vascular inflammation," "iliac and pudendal arteries dysfunction," "genitourinary tract," and "blood flow.", Main Outcome Measures: Management of systemic and local inflammation may be a useful alternative to improve SD and reduce the risk of cardiovascular diseases in the future., Results: Increased levels of cytokines and chemokines have been detected in humans and animals with hypertension, obesity, and diabetic conditions. Chronic activation of the innate immune system, especially by pathogen- or damage-associated molecular patterns, and metabolic-related disorders may act as triggers further contributing to an increased inflammatory condition. Due to the reduced size of vessels, SD and retinal vascular impairments have been shown to be predictive factors for cardiovascular diseases. Therefore, considering that blood flow to the genitalia is essential for sexual function, endothelial dysfunction and vascular remodeling, secondary to chronic immune system activation, may be implicated in male and female vasculogenic SD., Conclusions: Several conditions appear to play a role in SD. In the present review, we have identified a role for the immune system in generating vascular and tissue impairments contributing to erectile dysfunction and female SD. Calmasini FB, Klee N, Webb RC, et al. Impact of Immune System Activation and Vascular Impairment on Male and Female Sexual Dysfunction. Sex Med Rev 2019;7:604-613., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Morphological and physiological changes in the vasculature have been described in the evolution and maintenance of hypertension. Hypertension-induced vascular dysfunction may present itself as a contributing, or consequential factor, to vascular remodeling caused by chronically elevated systemic arterial blood pressure. Changes in all vessel layers, from the endothelium to the perivascular adipose tissue (PVAT), have been described. This mini-review focuses on the current knowledge of the structure and function of the vessel layers, specifically muscular arteries: intima, media, adventitia, PVAT, and the cell types harbored within each vessel layer. The contributions of each cell type to vessel homeostasis and pathophysiological development of hypertension will be highlighted.