atherogenesis Flashcards
What are the non-modifiable risk factors for arterial disease?
Genetic abnormalities
Family history
Increasing age
Being male
What are the modifiable risk factors for arterial disease?
Smoking
High blood pressure (hypertension)
High cholesterol levels
Diabetes mellitus
What are the components of the fibrous cap in an atheromatous plaque?
Smooth muscle cells
Foam cells
Macrophages
Lymphocytes
Proteoglycans
Collagen
Elastin
Neovascularization
What are the components of the necrotic core in an atheromatous plaque?
Cell debris
Cholesterol crystals
Calcium salts
Foam cells
What is the lipid hypothesis in atherogenesis?
The lipid hypothesis suggests a correlation between low cholesterol diet and low incidence of cardiovascular disease (CVD). CVD is linked to smoking, hypertension, and high blood cholesterol, specifically high LDL cholesterol.
What is the lipid oxidation hypothesis in atherogenesis?
The lipid oxidation hypothesis proposes that atherosclerosis is the consequence of free-radical-driven oxidative modification of LDL cholesterol. Oxidative stress, caused by reactive oxygen species like hydroxyl radicals, superoxide, and singlet oxygen, leads to the modification of LDL. Modified LDL is then taken up more rapidly by macrophages via non-specific scavenger receptors.
Is lipid oxidation the primary cause of atherosclerosis?
No, lipid oxidation is considered a contributing factor but not the primary cause of atherosclerosis.
What is the response to injury hypothesis in atherogenesis?
The response to injury hypothesis suggests that atherosclerosis is a chronic inflammatory response to endothelial injury. It involves various steps such as endothelial injury/dysfunction, lipoprotein accumulation, leukocyte adhesion and migration, foam cell formation, smooth muscle recruitment and proliferation, and extracellular matrix formation.
What are some causes of endothelial injury or dysfunction in atherogenesis?
Endothelial injury or dysfunction can be caused by haemodynamic stress (high blood pressure, arterial branch points), toxins (e.g., cigarette smoke), hyperlipidemia, and aging.
What is the endothelial injury response in atherogenesis?
The endothelial injury response involves the release of cytokines by endothelial cells and the expression of adhesion molecules. This allows leukocytes, specifically monocytes, to bind and infiltrate the endothelium, forming macrophages. The injury also leads to reduced nitric oxide (NO) production, which is important for maintaining endothelium-derived relaxing factor (EDRF) function.
What are some small molecules involved in atherosclerosis?
Cytokines: Small protein molecules that mediate/regulate inflammatory responses, e.g., IL-1, TNF-a, IFN-y.
Growth factors: Stimulate the growth of specific cell lines, e.g., PDGF, VSMGF.
Chemokines: Attract monocytes, e.g., MCP1.
Adhesion molecules: Play a role in leukocyte adhesion and migration, e.g., ICAM-1, VCAM-1.
How does lipoprotein accumulation contribute to atherosclerosis?
Common lipoprotein abnormalities lead to increased LDL cholesterol, reduced HDL cholesterol, and increased Lp(a). Endothelial injury causes increased oxygen free radicals and reduced nitric oxide (NO) levels. In the intima, two lipid forms accumulate: oxidized LDL and cholesterol crystals. These lipids stimulate the release of inflammatory mediators.
How are foam cells formed in atherosclerosis?
Oxidized lipids are ingested by macrophages, which leads to their transformation into foam cells.
What is the process of fatty streak formation in atherosclerosis?
Eventually, foam cells undergo apoptosis (programmed cell death). Smooth muscle cells migrate from the media and, along with foam cells, contribute to the formation of fatty streaks. Fatty streaks are visible in almost everyone from early teens, do not obstruct flow initially, but may progress over time.
How does plaque development and stabilization occur in atherosclerosis?
Smooth muscle cells (SMCs) migrate from the media and proliferate in response to the inflammatory environment. These SMCs synthesize extracellular matrix (ECM), mainly composed of collagen, elastin, and proteoglycans. The ECM helps stabilize the atherosclerotic plaque. The process is controlled by various cytokines and growth factors, including platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and tissue growth factor alpha (TGFa).
