Cardiovascular Health Flashcards
What is the endothelium?
The endothelium is a monolayer of endothelial cells lining the blood interface throughout the cardiovascular system including cardiac chambers
What is Cardiovascular Disease (CVD)?
CVD is a genera term for conditions affecting the heart and blood vessels such as atherosclerosis, hypertension, angina, myocardial infarction and stroke.
What is the function of the glycocalyx?
The glycocalyx (GX), is a carbohydrate-rich protective layer covering the ED, regulates permeability, control nitric oxide production and acts as a mechanosensor of blood shear stress.
Name some things that can damage the GX
The GX is easily damaged by inflammation, hyperglycaemia, endotoxemia, oxidised low-density lipoproteins and abnormal blood shear stress.
What does shear stress mean?
Shear stress is frictional force of blood on ED cells
Name the Key Functions of the endothelial
- Semi-permeable barrier:
Role of fluid balance, host
defence and movement of substances e.g. glucose and oxygen - Regulates vascular tone:
Secretes vasodilators e.g. NO and vasoconstrictors e.g. endothelin - Enzymes:
Contains angiotensin-converting enzyme (ACE) - plays a key role in regulating blood pressure - Angiogenesis:
ED cells are the origin of all new blood vessels - Haemostasis:
The luminal surface of ED prevents platelet adherence and coagulation - Immune defence:
Healthy ED cells deflect leukocyte adhesion and oppose local inflammation.
What is the role of Vascular Smooth Muscle cells? (VSMCs).
Located in the tunica media, VSMCs play a key role in vessel contraction and dilation (regulate blood circulation and pressure).
With the ED, VSMCs maintain the integrity and elasticity of blood vessels whilst limiting immune cell infiltration.
These changes are central to vascular disease, especially atherosclerosis and hypertension.
What role does Nitric Oxide play in cardiovascular health?
Regulates vascular tone, reduces platelet aggregation and VSMC proliferation, inhibits leukocyte adhesion and inflammatory cytokines and opposes oxidation of LDLs.
Name the amino acid that generates NO
L-arginine by the ED enzyme eNOS
Where does NO exert tis main physiological effect?
NO diffuses easily from the ED into VSMCs and the bloodstream, exerting its main physiological effects in large blood vessels
Which vitamin regulates NO synthesis?
Vitamin D, by mediating eNOS
What is the effect of oxidative stress and inflammation on the ED?
- increased permeability cytokines and leukocyte adhesion.
- Reduced vasodilator molecules.
- Increased risk of thrombosis
What is the effect of oxidative stress and inflammation on VSMCs?
- Increased inflammatory cytokines and extracellular matrix synthesis.
- Migration into the tunica intima and proliferation of VSMCs.
What are Peroxisome proliferator-activated receptors (PPARs)?
PPARs are nuclear transcription factors that control gene expression involved in adipogenesis, lipid and glucose metabolism, cellular proliferation and apoptosis .
What role do PPARs play in CVD?
PPARS decrease inflammation and promote ED health
PPARa activation increases HDL-C, decreases TG and inflammation and is anti-atherosclerosis.
Name some PPARa agonists
Green Tea
Resveratrol
Oregano
Thyme
Rosemary
Naringenin
Omega 3
Name some PPRA-y agonists and what they do
PPAR-y reduces blood glucose, fatty acids and insulin.
Natual PPAR-y agonists include:
apigenin
hesperidin
curcumin
resveratrol, EGCG (polyphenol from green tea).
Name some risk factors of CVD?
Family History
Siblings = 40% risk
Offspring of parents with premature CVD= 75% risk
Genetics:
MnSOD, NOS3, MTHRF and ACE
Ethnicity:
South Asian
Sub-Saharan African origin have enhanced risk
Gender:
Predominantly a male pathology but mortality is increasing in women
Name some of the vague physical symptoms of CVD in women
Lightheaded with exertion and heartburn
Name 3 other risk factors of CVD
Dyslipidaemia:
increases total cholesterol = increased LDL, VLDL, IDL, Lp(a). Decreased HDL: increased triglycerides
Hypertension:
CVD pathologies tend to appear 5 years earlier in those with hypertension.
Mitochondrial dysfunction:
ATP is required to pump ions out of myocardial cells, allows relaxation oand maintains electrochemical gradient across myocardial cell membrane.
Consider statins/CoQ10.
How does homocysteine play a role in CVD
Homocysteine is associated with LDL oxidation, monocyte adhesion and ED dysfunction.
Name some nutrient depletions that can be a risk factor for homocysteine
Low folate and B12 -
needed for re-methylation of homocysteine to methionine.
Vitamin B6 is a co-factor is conversion of homocysteine to cystein in the methylation cycle
How can genetic polymorphisms affect homocysteine levels
MTHFR needed to methylate B12 in methionine cycle.
FUT2, TCN impact B12 (all forms) absorption.
MTR, MTRR impact B12 activation
PEMT and CHDH and BHMT (betaine) are depended upon for methylation from other routes
How can changes in thyroid hormones have an impact on CVD?
Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue and minor TH changes can alter CV homeostasis. Hypo and hyperthyroidism are linked with ED dysfunction, dyslipidaemia and BP changes
/e
Explain how inflammation contributes to ED dysfunction
Inflammation has various origins including dyslipidaemia, dysbiosis and intestinal permeability, ROS, diabetes, excess adipose tissue and smoking.
In turn, ED dysfunction, subintimal cholesterol accumulation and recruitment of monocytes and T-cells drives inflammatory response.
In what way is obesity a risk factor for CVD?
Excess adipose tissue perpetuates inflammation contributing to vascular breakdown and metabolic complications
Adiponectin, a peptide that influences expression of ED cells, protecting against CVD is decreased in obesity.
Adiponectin also increases insulin sensitivity, thus low levels contribute to insulin resistance (IR).
Obesity is associated with high levels of leptin, which activates the SNS causing sodium retention, vasoconstriction and increases blood pressure
How does insulin resistance contribute to obesity (IR)
IR generates chronic hyperglycaemia leading to oxidative stress, inflammation and cellular damage
IR contributes to the lipid triad and dyslipidaemia.
Dyslipidaemia along with ED damage (due to dysfunctional insulin signalling) leads to athersclerotic plaque formation.
IR means that glucose is not cleared from the bloodstream as quickly as needed, increasing the risk of glycosylation reactions and the production of damaging compounds - Advanced glycation end products (AGEs)
What are AGES and explain how they contribute to CVD
AGEs are harmful compounds formed when protein or lipids become glycated after exposure to glucose. They exert their effects via tow main mechanisms
1. Receptor-mediated
2. Non-receptor mediated
This leads to oxidative stress, vascular ED and immune cell dysfunction.
Name some lifestyle risk factors for CVD
Smoking:
Increases oxidative stress and lowers antioxidants (1 cigarette= 25mg loss of vitamin C).
Nicotine increases Sympathetic Nervous System and increases blood pressure
Sedentary Lifestyle:
Exercise Increases insulin sensitivity and nitric oxide production. It has a positive effect on lipid profile and blood pressure
Chronic stress may cause ED dysfunction
Periodontal disease - increases systemic inflammation which impair vasodilation, promotes endothelial dysfunction, artierial stiffness and increases fibrinogen (plaque formation).
Heavy metals induce oxidative stress, lipid peroxidation and inflammatory cytokines. Cadmium and lead compete with zinc. A zinc deficiency increases atherosclerosis risk
Explain how the Gut-brain axis plays a role in CVD
SCFAs produced by the microbiota decrease risk of metabolic endotoxaemia by maintaining intestinal barrier integrity. SCFAs reduce serum lipids by inhibiting cholesterol synthesis or redirecting lipids to the liver.
What dietary considerations are risk factors for CVD
- High PRAL (potential renal acid load)
Foods rich in protein (e.g. meat and cheese) may induce low-grade metabolic acidosis, a risk factor for IR and CVD. - Trans fats promote dyslipaemia, increase inflammation, contribute to ED dysfunction, encourage visceral adiposity and increase risk of IR
- Fructose - high fructose intake promotes de nova iipogenesis, increase fatty acids, in particular palmitic acid. Palmitic acid is a major driver of atherosclerosis and CAD.
- Nutrient deficiences (e.g. vitamin C, D, E, CoQ10, magnesium)
Name 3 markers for Cardiovascular disease
- Cardiac risk tools
- Cardiac troponin
- Lipid profile
- Lp-PLA 2
- hsCRP
- MPO
How does a plant-based and Mediterranean-style diet reduce CVD risk
What is the RDA of Vitamin D for cardiovascular health
600-1000iu per day
Name 2 functions of Vitamin D in relation to CV health
- Modulates NO synthesis and influences cells involved in atherogenesis e.g. ED, VSMCs, monocytes and cardiac myocytes
- Modulates RAAS and lowers BP
What is the RDA of omega 3 in relation to CV
3-6 grams per day
What is the function of Omega 3 fatty acids in relation to CV health
- Improve lipid and lipoprotein profiles
- Involved in the synthesis of key regulators of inflammation, vasodilation and platelet aggregation.
- EPA stabilises cellular membranes allowing neutrilisation of extracellular ROS.
- DHA supports membrane fluidity
What is the recommended amount of Magnesium Glycinate/taurate in relation to CV health
500-800mg
Name 2 function of magnesium glycincate/ taurate
- Through regulation of ion transporters e.g. potassium and calcium channels plays a central role in modulating neuronal excitation, intracardiac conduction and myocardial contraction.
- Helps regulate vascular tone and stabilise heart rhythm.
