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vascular associated smooth muscle cell proliferation

Definition

Target type: biologicalprocess

The multiplication or reproduction of vascular smooth muscle cells, resulting in the expansion of a cell population. A vascular smooth muscle cell is a non-striated, elongated, spindle-shaped cell found lining the blood vessels. [PMID:23246467]

Vascular-associated smooth muscle cell (VSMC) proliferation is a crucial process for maintaining vascular homeostasis and responding to injury. It involves a complex interplay of signaling pathways, growth factors, and extracellular matrix components. The process can be divided into distinct phases:

1. **Initiation:**
- **Injury or stimuli:** VSMC proliferation is triggered by various stimuli, including vascular injury (e.g., atherosclerosis, hypertension), inflammation, and hypoxia. These stimuli activate specific signaling pathways, leading to the expression of growth factors and the release of inflammatory mediators.
- **Growth factor activation:** Growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor-beta (TGF-β) are released from damaged tissues or activated platelets. These factors bind to their receptors on VSMCs, initiating downstream signaling cascades.

2. **Cell cycle progression:**
- **Signal transduction:** Activated growth factor receptors trigger intracellular signaling pathways, including the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. These pathways stimulate the expression of cyclins and cyclin-dependent kinases (CDKs), which regulate cell cycle progression.
- **DNA replication and cell division:** Cyclins and CDKs promote the entry of VSMCs into the S phase of the cell cycle, allowing DNA replication. This is followed by mitosis (M phase), where the cell divides into two daughter cells.

3. **Termination:**
- **Growth factor withdrawal and inhibitory signals:** As the wound heals or the stimulus subsides, growth factor signaling decreases, and inhibitory signals like transforming growth factor-beta (TGF-β) become dominant.
- **Cell cycle arrest and apoptosis:** TGF-β and other inhibitory signals promote cell cycle arrest in the G1 phase and can induce apoptosis (programmed cell death) of VSMCs, preventing excessive proliferation.

4. **Extracellular matrix remodeling:**
- **Matrix metalloproteinases (MMPs):** VSMC proliferation is often accompanied by the expression and activation of MMPs, which degrade the extracellular matrix, allowing for cell migration and tissue remodeling.
- **New matrix deposition:** As the wound heals, VSMCs deposit new extracellular matrix components, contributing to tissue repair and vessel wall stabilization.

In addition to these core processes, VSMC proliferation is influenced by various factors, including:

* **Age and gender:** VSMC proliferation rates vary with age and sex.
* **Genetic factors:** Polymorphisms in genes involved in growth factor signaling and cell cycle regulation can influence the susceptibility to VSMC proliferation.
* **Lifestyle factors:** Smoking, diet, and exercise can influence VSMC proliferation and vascular health.

Dysregulation of VSMC proliferation contributes to various pathological conditions, including atherosclerosis, hypertension, restenosis after angioplasty, and vascular remodeling in response to chronic hypoxia. Understanding the complex molecular mechanisms underlying VSMC proliferation is essential for developing novel therapeutic strategies to prevent and treat these diseases.'
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Proteins (1)

ProteinDefinitionTaxonomy
Calcitonin gene-related peptide type 1 receptorA calcitonin gene-related peptide type 1 receptor that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16602]Homo sapiens (human)

Compounds (8)

CompoundDefinitionClassesRoles
haloperidolhaloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.

Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol
antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
azaperoneazaperone : An N-arylpiperazine that is 2-(piperazin-1-yl)pyridine in which the amino hydrogen is replaced by a 3-(4-fluobenzoyl)propyl group. Used mainly as a tranquiliser for pigs and elephants.

Azaperone: A butyrophenone used in the treatment of PSYCHOSES.
aminopyridine;
aromatic ketone;
monofluorobenzenes;
N-alkylpiperazine;
N-arylpiperazine;
tertiary amino compound
antipsychotic agent;
dopaminergic antagonist
telcagepanttelcagepant: structure in first source
mk 3207
bms 694153
(5s,6s,9r)-5-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5h-cyclohepta(b)pyridin-9-yl 4-(2-oxo-2,3-dihydro-1h-imidazo(4,5-b)pyridin-1-yl)piperidine-1-carboxylate
mk-8825
atogepantatogepant : A secondary carboxamide resulting from the formal condensation of the carboxy group of (3'S)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridine]-3-carboxylic acid with the amino group of (3S,5S,6R)-3-amino-6-methyl-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-2-one. It is a selective oral, small-molecule antagonist of calcitonin gene-related peptide (CGRP) receptor that has been approved for the treatment of migraine.azaspiro compound;
organic heterotetracyclic compound;
piperidones;
secondary carboxamide;
trifluorobenzene
calcitonin gene-related peptide receptor antagonist