Endothelial TRPV4–<scp>eNOS</scp> coupling as a vital therapy target for treatment of hypertension

Mao, Aiqin; Zhang, Peng; Ka, Zhang; Kan, Hao; He, Dongxu; Han, Xiping; Wang, Zhiwei; Tang, Chunlei; Ma, Xin

doi:10.1111/bph.15755

Cited by 16 publications

(13 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The potential validity of TRPV4 agonists or antagonists in cancer therapy needs more studies. Of note, systemic administration of TRPV4 agonists may have severe effects that preclude clinical application [159].…”

Section: Preclinical and Clinical Development Of Piezo1- Trpv4or Inte...mentioning

confidence: 99%

Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

et al. 2022

View full text Add to dashboard Cite

Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor and stromal cells to promote cancer cells proliferation, migration, invasion, angiogenesis and immune evasion. Both ECM itself and ECM stiffening-induced mechanical stimuli may activate cell membrane receptors and mechanosensors such as integrin, Piezo1 and TRPV4, thereby modulating the malignant phenotype of tumor and stromal cells. A better understanding of how ECM stiffness regulates tumor progression will contribute to the development of new therapeutics. The rapidly expanding evidence in this research area suggests that the regulators and effectors of ECM stiffness represent potential therapeutic targets for cancer. This review summarizes recent work on the regulation of ECM stiffness in cancer, the effects of ECM stiffness on tumor progression, cancer immunity and drug resistance. We also discuss the potential targets that may be druggable to intervene ECM stiffness and tumor progression. Based on these advances, future efforts can be made to develop more effective and safe drugs to interrupt ECM stiffness-induced oncogenic signaling, cancer progression and drug resistance.

show abstract

Section: Preclinical and Clinical Development Of Piezo1- Trpv4or Inte...mentioning

confidence: 99%

Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Primary endothelial cells were isolated from the thoracic aortas of 8-week-old male C57BL/6J mice and used in experiments without passage. 36 After the removal of adventitia, the thoracic aortas were digested with type IA collagenase (2 mg/mL) in HBSS for 20 minutes at 37 °C. The precipitated cells were centrifuged at 1200 revolutions per minute for 5 minutes and resuspended in endothelial complete medium with 1% endothelial cell growth supplement and 5% FBS.…”

Section: Methodsmentioning

confidence: 99%

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice

Liu

Luo

et al. 2023

ATVB

View full text Add to dashboard Cite

Background: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear. Methods: Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet–induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed. Results: We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a β-aminopropionitrile diet, Marfan mice with fibrillin-1 haploinsufficiency (Fbn1 C1041G/+ ), and ApoE −/− mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in β-aminopropionitrile–treated mice, Fbn1 C1041G/+ mice, and Ang II–infused ApoE −/− mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that FcγR (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated FcγR-mediated ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or FcγR deficiency. Conclusions: This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid–lowering drug may represent a promising therapeutic approach for TAAD.

show abstract

“…Of note, the TRPV1 channel was suggested to function not only as a Ca 2+ channel but also as a scaffold for the recruitment and formation of a complex comprising eNOS and key regulatory kinases, thereby providing necessary protein–protein interactions for the appropriate activation of eNOS [ 39 ]. Further, a functional complex between the TRPV4 channel and eNOS was described as important for proper endothelial functioning and vasodilation [ 40 ]. In addition, the amplification of Ca 2+ signaling in endothelial cells may occur via Piezo1/Pannexin1-mediated ATP release, where the latter activates purinergic receptors thereby augmenting Ca 2+ entry [ 32 , 38 , 41 ].…”

Section: No As a Key Vasorelaxing Factor In The Vasculaturementioning

confidence: 99%

The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis

Gaynullina

Tarasova

Shvetsova

et al. 2022

IJMS

View full text Add to dashboard Cite

The activity of many vasomotor signaling pathways strongly depends on extracellular/intracellular pH. Nitric oxide (NO) is one of the most important vasodilators produced by the endothelium. In this review, we present evidence that in most vascular beds of mature mammalian organisms metabolic or respiratory acidosis increases functional endothelial NO-synthase (eNOS) activity, despite the observation that direct effects of low pH on eNOS enzymatic activity are inhibitory. This can be explained by the fact that acidosis increases the activity of signaling pathways that positively regulate eNOS activity. The role of NO in the regulation of vascular tone is greater in early postnatal ontogenesis compared to adulthood. Importantly, in early postnatal ontogenesis acidosis also augments functional eNOS activity and its contribution to the regulation of arterial contractility. Therefore, the effect of acidosis on total peripheral resistance in neonates may be stronger than in adults and can be one of the reasons for an undesirable decrease in blood pressure during neonatal asphyxia. The latter, however, should be proven in future studies.

show abstract

Endothelial TRPV4–eNOS coupling as a vital therapy target for treatment of hypertension

Cited by 16 publications

References 61 publications

Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice

The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis

Contact Info

Product

Resources

About