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Role of microRNAs in Vascular Remodeling

View Article: PubMed Central - PubMed

ABSTRACT

Besides being involved in the gradual formation of blood vessels during embryonic development, vascular remodeling also contributes to the progression of various cardiovascular diseases, such as; myocardial infarction, heart failure, atherosclerosis, pulmonary artery hypertension, restenosis, aneurysm, etc. The integrated mechanisms; proliferation of medial smooth muscle cell, dysregulation of intimal endothelial cell, activation of adventitial fibroblast, inflammation of macrophage, and the participation of extracellular matrix proteins are important factors in vascular remodeling. In the recent studies, microRNAs (miRs) have been shown to be expressed in all of these cell-types and play important roles in the mechanisms of vascular remodeling. Therefore, some miRs may be involved in prevention and others in the aggravation of the vascular lesions. miRs are small, endogenous, conserved, single-stranded, non-coding RNAs; which degrade target RNAs or inhibit translation post-transcriptionally. In this paper, we reviewed the function and mechanisms of miRs, which are highly expressed in various cells types, especially endothelial and smooth muscle cells, which are closely involved in the process of vascular remodeling. We also assess the functions of these miRs in the hope that they may provide new possibilities of diagnosis and treatment choices for the related diseases.

No MeSH data available.


Related in: MedlinePlus

Modulation of proliferation, differentiation, inflammation or apoptosis by miR-21 in smooth muscle cells or endothelial cells. miR-21 is up-regulated by TGF-β and BMP and down-regulated in cells with serum withdrawal. The expression of miR-21 can increase the proliferation of smooth muscle cells through down-regulation of target genes, such as SP1, PTEN, SPRY1, or SPRY2 (fibroblast), or up-regulation of Bcl-2. Furthermore, miR-21 can up-regulate the differentiation of smooth muscle cells through down-regulation of PDCD4. In endothelial cells, miR induced apoptosis through down-regulation of PTEN and decreased the inflammation through targeting PPAR-α. Arrows (→) represent up-regulation. Capped lines (┤) indicate inhibition. Abbreviation: Aortic smooth muscle cell (ASMC), B cell leukemia/lymphoma 2 (Bcl-2), bone morphogenetic protein (BMP), cystathionine γ-lyase (CSE), Jun oncogene (AP-1), phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), monocyte chemotactic protein 1 (MCP-1), oscillatory shear stress (OSS), peroxisome proliferator activated receptor-α (PPAR-α), specificity protein-1 (SP1), sprouty homologue 1 (Spry1), transforming growth factor-β (TGF-β), unidirectional shear stress (USS), vascular cell adhesion molecule (VCAM).
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Figure 2: Modulation of proliferation, differentiation, inflammation or apoptosis by miR-21 in smooth muscle cells or endothelial cells. miR-21 is up-regulated by TGF-β and BMP and down-regulated in cells with serum withdrawal. The expression of miR-21 can increase the proliferation of smooth muscle cells through down-regulation of target genes, such as SP1, PTEN, SPRY1, or SPRY2 (fibroblast), or up-regulation of Bcl-2. Furthermore, miR-21 can up-regulate the differentiation of smooth muscle cells through down-regulation of PDCD4. In endothelial cells, miR induced apoptosis through down-regulation of PTEN and decreased the inflammation through targeting PPAR-α. Arrows (→) represent up-regulation. Capped lines (┤) indicate inhibition. Abbreviation: Aortic smooth muscle cell (ASMC), B cell leukemia/lymphoma 2 (Bcl-2), bone morphogenetic protein (BMP), cystathionine γ-lyase (CSE), Jun oncogene (AP-1), phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), monocyte chemotactic protein 1 (MCP-1), oscillatory shear stress (OSS), peroxisome proliferator activated receptor-α (PPAR-α), specificity protein-1 (SP1), sprouty homologue 1 (Spry1), transforming growth factor-β (TGF-β), unidirectional shear stress (USS), vascular cell adhesion molecule (VCAM).

Mentions: miR-21 is expressed in fibroblasts [23], cardio-myocytes [24], and endothelial cells [25]. In these cells, the function of miR-21 is to regulate fibrosis in fibroblasts, apoptosis in cardiomyocytes, and cell proliferation, migration, and tubulogenesis in endothelial cells. Knockdown of miR-21 may inhibit cardiac fibrosis and alleviate the detrimental effects of cardiac fibrosis. Therefore, the knockdown of miR-21 is a potential therapeutic strategy for the treatment of cardiac fibrosis [23]. Cardiac fibrosis involves vascular remodeling and is characterized by the proliferation of cardiac fibroblasts and extracellular matrix (ECM) deposition in the myocardial interstitial space. This can impair the correct functioning of heart [26]. Cardin et al. found that over-expression of miR-21 targeted Sprouty-1 [27], and Thum et al. also found that it up-regulated the phosphorylation of MAPK inducing increased fibrosis [28] (Fig. 2).


Role of microRNAs in Vascular Remodeling
Modulation of proliferation, differentiation, inflammation or apoptosis by miR-21 in smooth muscle cells or endothelial cells. miR-21 is up-regulated by TGF-β and BMP and down-regulated in cells with serum withdrawal. The expression of miR-21 can increase the proliferation of smooth muscle cells through down-regulation of target genes, such as SP1, PTEN, SPRY1, or SPRY2 (fibroblast), or up-regulation of Bcl-2. Furthermore, miR-21 can up-regulate the differentiation of smooth muscle cells through down-regulation of PDCD4. In endothelial cells, miR induced apoptosis through down-regulation of PTEN and decreased the inflammation through targeting PPAR-α. Arrows (→) represent up-regulation. Capped lines (┤) indicate inhibition. Abbreviation: Aortic smooth muscle cell (ASMC), B cell leukemia/lymphoma 2 (Bcl-2), bone morphogenetic protein (BMP), cystathionine γ-lyase (CSE), Jun oncogene (AP-1), phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), monocyte chemotactic protein 1 (MCP-1), oscillatory shear stress (OSS), peroxisome proliferator activated receptor-α (PPAR-α), specificity protein-1 (SP1), sprouty homologue 1 (Spry1), transforming growth factor-β (TGF-β), unidirectional shear stress (USS), vascular cell adhesion molecule (VCAM).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384354&req=5

Figure 2: Modulation of proliferation, differentiation, inflammation or apoptosis by miR-21 in smooth muscle cells or endothelial cells. miR-21 is up-regulated by TGF-β and BMP and down-regulated in cells with serum withdrawal. The expression of miR-21 can increase the proliferation of smooth muscle cells through down-regulation of target genes, such as SP1, PTEN, SPRY1, or SPRY2 (fibroblast), or up-regulation of Bcl-2. Furthermore, miR-21 can up-regulate the differentiation of smooth muscle cells through down-regulation of PDCD4. In endothelial cells, miR induced apoptosis through down-regulation of PTEN and decreased the inflammation through targeting PPAR-α. Arrows (→) represent up-regulation. Capped lines (┤) indicate inhibition. Abbreviation: Aortic smooth muscle cell (ASMC), B cell leukemia/lymphoma 2 (Bcl-2), bone morphogenetic protein (BMP), cystathionine γ-lyase (CSE), Jun oncogene (AP-1), phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), monocyte chemotactic protein 1 (MCP-1), oscillatory shear stress (OSS), peroxisome proliferator activated receptor-α (PPAR-α), specificity protein-1 (SP1), sprouty homologue 1 (Spry1), transforming growth factor-β (TGF-β), unidirectional shear stress (USS), vascular cell adhesion molecule (VCAM).
Mentions: miR-21 is expressed in fibroblasts [23], cardio-myocytes [24], and endothelial cells [25]. In these cells, the function of miR-21 is to regulate fibrosis in fibroblasts, apoptosis in cardiomyocytes, and cell proliferation, migration, and tubulogenesis in endothelial cells. Knockdown of miR-21 may inhibit cardiac fibrosis and alleviate the detrimental effects of cardiac fibrosis. Therefore, the knockdown of miR-21 is a potential therapeutic strategy for the treatment of cardiac fibrosis [23]. Cardiac fibrosis involves vascular remodeling and is characterized by the proliferation of cardiac fibroblasts and extracellular matrix (ECM) deposition in the myocardial interstitial space. This can impair the correct functioning of heart [26]. Cardin et al. found that over-expression of miR-21 targeted Sprouty-1 [27], and Thum et al. also found that it up-regulated the phosphorylation of MAPK inducing increased fibrosis [28] (Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

Besides being involved in the gradual formation of blood vessels during embryonic development, vascular remodeling also contributes to the progression of various cardiovascular diseases, such as; myocardial infarction, heart failure, atherosclerosis, pulmonary artery hypertension, restenosis, aneurysm, etc. The integrated mechanisms; proliferation of medial smooth muscle cell, dysregulation of intimal endothelial cell, activation of adventitial fibroblast, inflammation of macrophage, and the participation of extracellular matrix proteins are important factors in vascular remodeling. In the recent studies, microRNAs (miRs) have been shown to be expressed in all of these cell-types and play important roles in the mechanisms of vascular remodeling. Therefore, some miRs may be involved in prevention and others in the aggravation of the vascular lesions. miRs are small, endogenous, conserved, single-stranded, non-coding RNAs; which degrade target RNAs or inhibit translation post-transcriptionally. In this paper, we reviewed the function and mechanisms of miRs, which are highly expressed in various cells types, especially endothelial and smooth muscle cells, which are closely involved in the process of vascular remodeling. We also assess the functions of these miRs in the hope that they may provide new possibilities of diagnosis and treatment choices for the related diseases.

No MeSH data available.


Related in: MedlinePlus