Inflammation And CAD Flashcards
Inflammation contributes to what heart disease
Atherosclerosis (Coronary, cerebral, Peripheral vascular disease)
5x higher risk when you reach 40yo-60yo
Atherosclerosis risk factors that are non changeable
- XY
- Genetics
- Age
- FH
Atherosclerosis risk factors that are changeable
- Hyperlipidemia
- HTN
- Diabetes
- Obesity
- Chronic inflammation
- Smoking
- VIT deficiency (B6)*
- Sedentary lifestyle
5 stages of Atherosclerosis happening
- Chronic endothelial injury (from any risk factor, toxins, virus)
- Endothelial Dysfunction: increased permeability of leukocytes
- Macrophages are activated (SM is recruited)
- M and SM trap lipids
- SM proliferates (ECM has lipids and grows)
What does the endothelial injury cause
Usually from risk factors
It causes chronic inflammation to repair the tissue
* most common from HTN and hyperlipidemia
Where does atherosclerosis happen most likely
Opening of exiting vessels, branch points, and posterior abd aorta
= these locations have flow disturbances (HEMODYNAMIC TURBULENCE)**
Endothelial Dysfunction is when
There is a chronic injury due to risk factor present
——> permanent permeability increased for leukocytes, monocytes
= inflammatory response
Stage 1 injury to endothelium causes what
Endothelium altered and expresses adhesion molecules, pro inflammatory cytokines, procoagulators
= initiates thrombus formation , atherosclerosis, vascular lesions
Basal endothelial cells
Non-thrombogenic, keeps blood fluid
Mediate SM to increase resistance
SM in vessels
Vascular repair and atherosclerosis
Can proliferate and make collagen, cytokines
Dilate and constrict vessels
What do IL-1 and TNF do
Increase P and E selectins on endothelium
Increase ligand on leukocytes
(Rolling of leukocytes)=slows them so they can attach, cluster and flatten to cross the endothelium
= large inflammation in ECM (IL-6 and IL1 and TNF, brings pro inflammatory)
Long term increase in IL 1 and TNF causes
Increased dilation = increased turbulence in the vessels
Brings proteins close to the damaged organs
Which proteins are brought to the sight of damaged organ
- Clotting protein
- Complement proteins
- Kinin cascade (dilation, increase permeability, pain receptors)
- Fibrinolytic protein (degrade clot when wound is healed)
What happens when the endothelium dysfunction has happened for a while
Macrophages enter the area causing SM thickening
Circulating lipids do what at these inflammed sites
They deposited in intima and phagocyted by M and modified
* modified to toxic LDL incident the M and SM cells
= stimulation of foam cells in these lesions ——> FATTY STREAK
Atheroma
Atheromatous ——> atherosclerotic plaques
What are CD36 scavenger receptors
M and monocytes have these to OXIDIZE LDL
Can also happen when binding to TLR4
Oxidization of LDL has what types of cells
M1, IL1, IL6, CRP, Fibrinogen, Serum Amyloid A, C protein, plasminogen
M2 is in the plaques
Inflammasome
Foam cells and cholesterol crystals form these when LDL is present and is oxidized
They make IL1, IL8 = INFLAMMATION
Neutrophils NETosis
They release their NETs that provide platelets scaffolding, RBC activation, thrombosis
Also stimulates the M
Inflammation at the foam cells and NETosis site causes what
SM cells recruitment and proliferation that make COLLAGEN (ECM)
What stimulates SM proliferation
PDGF
FGF
TGF-a
SM can also (lipids)
Phagocytosis LDL
T cells effect on atherosclerosis
T cells are presented to the modified LDL by M and DCs
——> vascular inflammation
