positive regulation of vascular associated smooth muscle cell proliferation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. [GO_REF:0000058, GOC:TermGenie, PMID:23246467]

Positive regulation of vascular associated smooth muscle cell proliferation is a complex process that involves a series of tightly regulated molecular events. This process plays a crucial role in the maintenance of vascular homeostasis and the repair of injured blood vessels.

**Key signaling pathways and molecular events:**

* **Growth factors:** Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF) are key mitogens that stimulate smooth muscle cell proliferation.
* **Cytokines:** Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta) can also influence smooth muscle cell proliferation, depending on the context.
* **Receptor tyrosine kinases (RTKs):** Growth factors bind to and activate specific RTKs on smooth muscle cells, leading to downstream signaling cascades. For example, PDGF binds to PDGFR, VEGF binds to VEGFR, and FGF binds to FGFR.
* **MAPK signaling pathway:** Activation of RTKs leads to activation of the mitogen-activated protein kinase (MAPK) signaling pathway. This pathway involves a series of kinases, including Ras, Raf, MEK, and ERK, which ultimately activate transcription factors that promote cell cycle progression.
* **PI3K/AKT signaling pathway:** Activation of RTKs also activates the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. AKT phosphorylates and activates downstream targets, including mTOR, which promotes protein synthesis and cell growth.
* **Cyclin-dependent kinases (CDKs):** CDKs are a family of enzymes that regulate the cell cycle by controlling the progression through different phases. CDKs are activated by cyclins, which are proteins whose expression is tightly regulated during the cell cycle.
* **Transcription factors:** Various transcription factors are activated by signaling pathways, including the MAPK and PI3K/AKT pathways. These transcription factors bind to specific DNA sequences, regulating the expression of genes involved in cell cycle progression, proliferation, and differentiation.

**Role of extracellular matrix (ECM):**

* The ECM provides structural support and signaling cues to smooth muscle cells.
* Components of the ECM, such as fibronectin and collagen, can bind to integrins on smooth muscle cells, activating intracellular signaling pathways that influence proliferation.
* ECM degradation can also release growth factors and cytokines that promote smooth muscle cell proliferation.

**Regulation of proliferation:**

* **Cell-cell interactions:** Smooth muscle cells can interact with each other and with other cell types in the vascular wall, influencing their proliferation.
* **Mechanical forces:** Stretch and shear stress can modulate smooth muscle cell proliferation, depending on the magnitude and duration of the force.
* **Immune response:** Immune cells, such as macrophages and T lymphocytes, can release cytokines and chemokines that influence smooth muscle cell proliferation.

**Implications for vascular disease:**

* Dysregulation of positive regulation of vascular associated smooth muscle cell proliferation is implicated in various vascular diseases, including atherosclerosis, hypertension, and restenosis.
* Overproliferation of smooth muscle cells can lead to narrowing of blood vessels, increasing the risk of cardiovascular events.
* Therapies targeting specific signaling pathways or molecular targets involved in this process may offer potential therapeutic benefits for treating vascular diseases.'
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Proteins (26)

Compounds (678)