Serum Amyloid A Induces a Vascular Smooth Muscle Cell Phenotype Switch through the p38 MAPK Signaling Pathway

Zhang, Xincai; Chen, Jinqin; Wang, Shixun

doi:10.1155/2017/4941379

Cited by 29 publications

(30 citation statements)

References 27 publications

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“…In addition, the acute-phase proteins serum amyloid A and C-reactive protein have been reported not to be solely produced by hepatocytes, but also in the arterial wall, by vascular smooth muscle cells (VSMCs). Both proteins stimulate the phenotypic switch of VSMCs into bone-like cells through activation of the p38 MAPK pathway and oxidative stress pathways [31,32]. As mentioned above, our study also revealed that, after proteomic analysis of aortic tissue from either IS or PCS exposed CKD rats, coagulation pathways (intrinsic/extrinsic prothrombin activation pathways) play a central role in the arterial calcification process [21].…”

Section: Inflammation and Coagulation Signaling Pathwayssupporting

confidence: 68%

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

Opdebeeck

D’Haese

Verhulst

2020

Toxins

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The protein-bound uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are considered to be harmful vascular toxins. Arterial media calcification, or the deposition of calcium phosphate crystals in the arteries, contributes significantly to cardiovascular complications, including left ventricular hypertrophy, hypertension, and impaired coronary perfusion in the elderly and patients with chronic kidney disease (CKD) and diabetes. Recently, we reported that both IS and PCS trigger moderate to severe calcification in the aorta and peripheral vessels of CKD rats. This review describes the molecular and cellular mechanisms by which these uremic toxins induce arterial media calcification. A complex interplay between inflammation, coagulation, and lipid metabolism pathways, influenced by epigenetic factors, is crucial in IS/PCS-induced arterial media calcification. High levels of glucose are linked to these events, suggesting that a good balance between glucose and lipid levels might be important. On the cellular level, effects on endothelial cells, which act as the primary sensors of circulating pathological triggers, might be as important as those on vascular smooth muscle cells. Endothelial dysfunction, provoked by IS and PCS triggered oxidative stress, may be considered a key event in the onset and development of arterial media calcification. In this review a number of important outstanding questions such as the role of miRNA’s, phenotypic switching of both endothelial and vascular smooth muscle cells and new types of programmed cell death in arterial media calcification related to protein-bound uremic toxins are put forward and discussed.

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Section: Inflammation and Coagulation Signaling Pathwayssupporting

confidence: 68%

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

Opdebeeck

D’Haese

Verhulst

2020

Toxins

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“…Results suggest that the activated p38MAPK signaling pathway plays a key role in the process of transformation of the VSMC phenotype from the dedifferentiated to differentiated state [56]. Some findings implied that the proliferative ability of VSMCs was also increased by serum amyloid (SAA) treatment via activation of p38 MAPK [57]. However, existing evidence shows that VSMC phenotypic switching was inhibited by pretreatment with the inhibitor of p38 MAPK [58].…”

Section: Discussionmentioning

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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“…6 While a detailed discussion of the mechanisms of myelin-associated inhibition of axonal outgrowth is outside the scope of this review, we refer the reader to a review by Zhang et al for more information. 23 There is also an accumulation of extracellular amino acids at the site of injury, whose abundance relates to severity of SCI and neurotoxicity. 22 These molecules are attractive targets for pharmacological intervention aimed at enhancing neuroprotection and neuroregeneration post-SCI and are discussed more in the following sections.…”

Section: Figmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

121

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Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions.

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Serum Amyloid A Induces a Vascular Smooth Muscle Cell Phenotype Switch through the p38 MAPK Signaling Pathway

Cited by 29 publications

References 27 publications

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

Molecular and Cellular Mechanisms that Induce Arterial Calcification by Indoxyl Sulfate and P-Cresyl Sulfate

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

Regenerative Therapies for Spinal Cord Injury

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