Akt/eNOS and MAPK Signaling Pathways Mediated the Phenotypic Switching of Thoracic Aorta Vascular Smooth Muscle Cells in Aging/Hypertensive Rats

Zhang, Lin; Xu, Zhaoxia; Ying, Wantao; Liao, Jingwen; Zeng, Fanxing; Shi, Lijun

doi:10.33549/physiolres.933779

Cited by 20 publications

(10 citation statements)

References 39 publications

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“…Angiotensin II activates its receptor on the endothelial cell surface triggering formation of reactive oxygen species and activation of several intracellular pathways like MAPK (ERK1/2) and others (Akt, NF-kB, MMPs) (87). A large number of transcription factors are then activated or repressed leading to fibroblast-to-myofibroblast activation, myocyte growth, vascular smooth muscle cell phenotype switching, inflammation, and fibrosis (88,89). In addition to neurohumoral activation, high blood pressure causes direct mechanical stress which can activate the MAPK pathway via various cell-surface proteins (85).…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

Langlo

Silva

Overrein

et al. 2021

Front. Cardiovasc. Med.

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There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75–0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

Langlo

Silva

Overrein

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

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“…Furthermore, OPN is regulated by the SASP regulator C/EBPβ [69], and Lee et al [70] suggested that hydroxynonenal (HNE) induced OPN expression in HVSMCs via signaling pathways involving AP-1 and C/EBPβ, increasing HVSMCs proliferation and vascular remodeling. Another study demonstrated that hypertension and senescence had a compounding effect on the vascular system and induced OPN expression via the PI3K/ AKT/eNOS and Ras/Raf/MAPK signaling pathways [71].…”

Section: Osteopontinmentioning

confidence: 99%

The emerging role of cell senescence in atherosclerosis

Zheng

Wang

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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Cell senescence is a fundamental mechanism of aging and appears to play vital roles in the onset and prognosis of cardiovascular disease, fibrotic pulmonary disease, liver disease and tumor. Moreover, an increasing body of evidence shows that cell senescence plays an indispensable role in the formation and development of atherosclerosis. Multiple senescent cell types are associated with atherosclerosis, senescent human vascular endothelial cells participated in atherosclerosis via regulating the level of endothelin-1 (ET-1), nitric oxide (NO), angiotensin II and monocyte chemoattractant protein-1 (MCP-1), senescent human vascular smooth muscle cells-mediated plaque instability and vascular calcification via regulating the expression level of BMP-2, OPN, Runx-2 and inflammatory molecules, and senescent macrophages impaired cholesterol efflux and promoted the development of senescent-related cardiovascular diseases. This review summarizes the characteristics of cell senescence and updates the molecular mechanisms underlying cell senescence. Moreover, we also discuss the recent advances on the molecular mechanisms that can potentially regulate the development and progression of atherosclerosis.

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“…According to experimental data, extracellular signal-regulated (ERK) and p38 MAPK are involved in VSMC phenotype switching, but Jun N-terminal kinase (JNK) is a different story [28,29]. In our previous study, cross-talk occurred between the Akt and MAPK pathways during phenotype switching in aging and hypertensive rats [30].…”

Section: Introductionmentioning

confidence: 99%

Role of the Balance of Akt and MAPK Pathways in the Exercise-Regulated Phenotype Switching in Spontaneously Hypertensive Rats

Zhang

Ying

et al. 2019

IJMS

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The mechanisms regulating vascular smooth muscle cell (VSMC) phenotype switching and the critical signal modulation affecting the VSMCs remain controversial. Physical exercise acts as an effective drug in preventing elevated blood pressure and improving vascular function. This study was designed to explore the influence of aerobic exercise on the suppression of VSMC phenotype switching by balancing of the Akt, also known as PKB (protein kinase B) and mitogen-activated protein kinase (MAPK) signaling pathways. Spontaneously hypertensive rats (SHRs) and normotensive rats were subjected to exercise treatment before measuring the vascular morphological and structural performances. Exercise induced reverse expression of VSMC protein markers (α-SM-actin, calponin, and osteopontin (OPN)) in spontaneously hypertensive rats. It is noteworthy that the low expression of phosphorylated Akt significantly decreased the expression of VSMC contractile phenotype markers (α-SM-actin and calponin) and increased the expression of the VSMC synthetic phenotype marker (OPN). However, the MAPK signal pathway exerts an opposite effect. VSMCs and whole vessels were treated by inhibitors, namely the p-Akt inhibitor, p-ERK inhibitor, and p-p38 MAPK inhibitors. VSMC phenotype markers were reversed. It is important to note that a significant reverse regulatory relationship was observed between the expression levels of MAPK and the contractile markers in both normotensive and spontaneously hypertensive rats. We demonstrate that aerobic exercise regulates the VSMC phenotype switching by balancing the Akt and MAPK signaling pathways in SHRs.

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Akt/eNOS and MAPK Signaling Pathways Mediated the Phenotypic Switching of Thoracic Aorta Vascular Smooth Muscle Cells in Aging/Hypertensive Rats

Cited by 20 publications

References 39 publications

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

The emerging role of cell senescence in atherosclerosis

Role of the Balance of Akt and MAPK Pathways in the Exercise-Regulated Phenotype Switching in Spontaneously Hypertensive Rats

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