L2: Inflammation & Cardiovascular disease

Question 1

What is inflammation?

Answer 1

Localised immune response to physical injury or infection, characterised by redness, swelling, pain and heat.

Question 2

What are the functions of inflammation?

Answer 2

1) Destroy infected and damaged tissue via phagocytic cells
2) Stimulate tissue repair via cytokines to release repair proteins such as C-reactive protein and fibrinogen from the liver.

Question 3

When is inflammation bad?

Answer 3

Chronic low-grade inflammation that leads to repair dysfunction

Question 4

What causes Chronic inflammation?

Answer 4

1) Hypoxia or tissue damage
2) Free fatty acid uptake by immune cells
3) High level of toxin circulation or infection

Question 5

How does positive energy balance lead to chronic inflammation?

Answer 5

1. Increased FFA storage in adipocytes causes hypertrophy to occur.
2. Enlargement of adipocytes imposed a hypoxic condition which initiates an inflammatory response. M2 macrophages are replaced with M1 and T-cells become activated.
3. Pro-inflammatory cytokines such as IL-6 and TNF-alpha are released
4. Recovery requires long term responses such as angiogenesis, meaning pro-inflammatory state is chronically.

Question 6

What disease are associated with chronic inflammation?

Answer 6

1. Heart disease
2. Diabetes
3. Dementia
4. Arthritis
5. Multiple sclerosis
6. Stroke
7. Chronic obstructive pulmonary disease

Question 7

What roles does IL-6 have in promoting chronic disease

Answer 7

1. Insulin sensitivity decreases
2. Increased macrophage lipid uptake which increases foam cells and fatty streak formation (Atherosclerosis)
3. Endothelial stickiness increasing thrombus formations
4. Increased platelet sticking increasing clot formation.

Question 8

What roles does C-reactive protein have in promoting chronic disease?

Answer 8

1. Increased clot formation
2. Increased FA oxidation which leads to increased Macrophage engulf leading to increase cytokine release
3. Increase macrophage adhesion molecule expression promoting localised accumulation of inflammation.

Question 9

Where is IL-6 predominantly released from?

Answer 9

Adipocytes

Question 10

What is the biggest risk factor for inflammation?

Answer 10

Obesity

Question 11

What study identified the importance of inflammation in developing cardiovascular disease?

Answer 11

Ridker et al, 2017: Used drugs which targets IL-1B pathway to reduce levels of CRP on patients who have previously had a heart attack and CRP >2mg.L and identified that lower cardiovascular events where associated with lower CRP levels.

Question 12

Explain the study that identified the relationship between physical activity and pro-inflammation.

Answer 12

Vella et al, 2017: Measured physical activity and pro-inflammatory markers of 2000 individuals along with visceral and subcutaneous adiposity. Identified that increased moderate-vigerous activity decreased pro-inflammatory molecules. This is partly explained by reduced adiposity from increased exercise but also identifies that exercise has a direct effect in reducing pro-inflammatory molecules associated with increased chronic disease and all-cause mortality.

Question 13

What longitudinal study looked at the effect of physical activity and pro-inflammatory IL-6 and CRP?

Answer 13

Hamer et al, 2012: 50% of individuals where prescribe physical activity exercise guidelines, those that maintained physical activity after 10 years had lower levels of IL-6 and CRP despite increases due to age and irrespective of adiposity.

Question 14

What are the mechanisms in which physical activity provides anti-inflammatory effects.

Answer 14

1. Reduced adipocyte size and quantity in response to physical exercise, reduces the release of IL-6.
2. Exercise reduces macrophage entry into adipocytes, thus preventing IL-6 secretion
3. Immune cell characteristics change to a more anti-inflammatory cytokine profile (TNF-a & IFN-Y decrease and TGF-B and IL-4 increase)
4. Exercise reduces endothelial adhesion molecules responsible for monocyte intake into the tunica media. Subsequently less macrophages are available to produce pro-inflammatory molecules
   5) During >60% vo2max muscle cells release upwards of 20 fold IL-6 which triggers a compensatory release of anti-inflammatory molecules that are longer lasting. Net outcome of anti-inflammatory response.

Question 15

What are the biological effects of IL-6 from muscle?

Answer 15

1. Increased glycogenolysis, lipolysis, fat oxidation and Anti-inflammatory IL-10 and IL-1ra and decreased Tryacylgylerides associated with reduced risk of T2DM.
2. Supresses inflammation by releasing IL10 and IL-1ra which stay in the system for longer. Decreasing the risk of inflammatory disease such as cardiovascular disease, rheumatic arthritis. Muscle does this in high levels

Question 16

What was one of the factors the MESA study identified?

Answer 16

Adiponectin is increased in response to physical activity. This is achieved from an higher reduction in visceral fat leaving a larger proportion of subcutaneous adipose tissue. Subcutaneous fat releases higher levels of adiponectin and so the proportion of adiponectin is higher.

Question 17

What is adiponectin

Answer 17

A hormone responsible for glucose metabolism by regulating cell sensitivity to insulin.

Question 18

How does obesity effect adiponectin levels

Answer 18

Adiponectin levels are lower in obese individuals and thus contributes to insulin resistance seen in T2DM

Question 19

How else does exercise reduce inflammation?

Answer 19

Exercise causes blood volume expansion and improves haemoglobin oxygen affinity. Thus, a reduction in adipose hypoxia occurs, reducing the inflammatory response caused by M1 macrophages and activated t-cells.
The increase oxygen concentration also elevates angiogenesis further improving oxygen availibility to adipocytes and reducing low grade chronic inflammation.