Week 7 inflammation and CVD Flashcards
Inflammation is a necessary response, what is it?
Local immune response to physical injury / damage (cell or tissue) or infection
Redness, pain, swelling
Influx of immune cells to the area to repair damage
Increased blood flow to area
Pain receptors stimulated
What are the functions of inflammation?
To destroy infected/damaged tissue (phagocytic cells - engulf and destroy the target)
Stimulate tissue repair
How does inflammation stimulate tissue repair?
Cytokines released by immune cells (in the tissues), endothelial cells and adipocytes stimulate the liver to release acute phase proteins such as C-reactive protein (CRP) and fibrinogen (repair proteins).
Chronic low grade inflammation can end up damaging healthy tissues, what are some causes of this?
Activation within tissues in response to tissue damage / hypoxia (e.g. from obesity)
Free fatty acid uptake by immune cells - activates immune cells - release more inflammatory cytokines
Infection
What is tissue hypoxia?
Positive energy balance and physical inactivity leads to increased size of adipocytes
The same blood supple therefore has to supply an increased SA so tissue hypoxia occurs
Immune cells see this as a danger / injury and initiate an inflammatory response.
What does tissue hypoxia lead to (primary)?
An increase in pro-inflammatory adipokines (cytokines from adipose tissue)
Increase in triglycerides and LDL
Increased FFA also activates immune cells (TLR expression).
What does tissue hypoxia lead to (secondary)?
Chronic low grade inflammation
Increased risk for atherosclerosis, T11 diabetes, neurodegeneration and tumour growth
Reduced functional capacity
Reduced longevity
What are some of the diseases associated with chronic low grade inflammation?
Multiple sclerosis Stroke Some cancers Rheumatoid arthritis Heart disease Kidney disease T11 diabetes Dementia Pulmonary disease
What act as markers of of chronic low grade inflammation?
Increases in circulating pro inflammatory cytokines and acute phase proteins
However, as well as being markers they are often involved themselves and can also make things worse
What are some examples of pro inflammatory cytokines?
Interlukin (IL-6) (IL-1B)
Tumour necrosis factor (TNF-d) (however, these are broken down quickly in the circulation so not as reliable a measure).
Summarise the main effects of IL-6
Reduced tissue insulin sensitivity (related to T11D)
Increases the amount of fat that immune cells take up - activates them - increases more cytokines
Increased macrophage lipid uptake
Increased endothelial ‘stickiness’ - increases risk of clot formation and helps inflammatory immune cells move into the tissues
Increased platelet clotting
Summarise the main effects of CRP
Increased clot formation
Increased FA oxidation within immune cells - produce more IL-6
Increased macrophage FA uptake
Increased macrophage adhesion molecule expression - more likely to stick to blood vessel walls / move into tissues
Is muscle damage a cause of acute or chronic inflammation?
Acute
Summarise the study by Bermudez et al (2002) looking at IL-6 and risk factors for CVD in apparently healthy women
Risk factors looked at; Age >60yrs Current smoker Sedentary lifestyle BMI >27Kg/m2 SBP >140mmHg Presence of diabetes
Found that the more risk factors you had the higher IL-6 tended to be
Also found the same association with CRP
Some medication can block the IL-1B pathway, what are the key findings of this?
Lowered CRP but not lipids
Reduced incidence of another CV event after 4 years
