Cardiovascular ageing: epidemiology
14 important questions on Cardiovascular ageing: epidemiology
What are NAD+ precursors [caloric restriction mimetics]
NAD+ is a coenzyme that is found and needed in all living cells. Here outlined in red is the niconanamide group, which can exit in two forms: the oxidized form NAD+ and the reduced form NADH. In metabolism, NAD+ can accept electrons, NADH can donate electrons in the redox reactions and thus is necessary for ATP production.
What is the role of NAD in Cardiac Energy Metabolism?
We have talked about this 3 components of the cardiac energy metabolism. Component 1 and 2 are the steps that generate ATP. NAD is needed for 1st component and NADH is needed for the 2nd component.
Is NAD+ declining with ageing?
You can image that if NAD+ is decrased, the energy production will be decreased too. Indeed, as you see from this figure, NAD+ and ATP levels is measure in different ages of mice 6-, 22-, and 30-month-old mice (n = 5, *p < 0.05 versus 6-month-old mice). ATP content of 6-, 22-, and 30-month-old mice (n = 5, *p < 0.05 versus 6-month-old mice). You can see clearly reduction of NAD+ as well as ATP levels in the aged mice.
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How to prevent NAD+ with ageing with diet or nutrition.
the role of NAM in the preventing the age-related diastolic dysfunction and also the diastolic heart failure also called HFpEF.
Where is a higher dietary NAD+ intake associated with?
they also measure the NAD contact in the human heart. They found a rduction of NAD+ in HEpEF pateints. And also the dietatry intake of the vitabmin B3 (niacin) reduced the risk for mortality especially the cardiac mortality. (In the ageing population, cardiac vascular disease is the no.1 cause of death)
What are the risks factors and consequences of AF?
- ageing
- obesity
- diabetes
- hypertension
- valvular heart disease
consequences
- stroke
- heart failure
- death
- decrease the quality of life of the patients, they often may feel palpitation (=hartkloppingen) and have exercise intolerence.
In the clinics, doctors clasify the patients into 4 groups based on the duration of AF episodes. What are these classifications?
- Normal
- Paroxysmal (< 1 week)
- Persistent (>1 week (week to months))
- Long standing persistent (>12 months)
- Permanent (not treatable)
currently patients can be treated with electrical cardioversion or pharmacological drugs, but these treatments are only symptomatic treatment, meaning they can only targeting the symptoms such as to slow down the heart rate or restore heart rhythm. These treatment only works for a short period. It does not stop the progression of the disease. Often, patients comes back to the clinics as AF recur.
- electrical cardio version
- pharmacological cardio version
What are the causes of atrial remodelling
- 'lone' AF [<2%]
- risk factors [>98%]
When/where do these thee types of atrial remodelling take place?
- electrical remodelling
- structural remodelling
- metabolic remodelling
The first signs of structural remodelling do not become apparent until several weeks later.
The period in between (which coincides with a major increase in AF stabilization) is likely to be the most important phase of metabolic remodelling, hallmarked by chronic supply–demand ischaemia and hypoxia. Changing patterns of gene expression in this period reflect a reorientation of metabolism, regression to a foetal phenotype and hibernation.
What does the electrical remodelling do?
You see decreased of CaT amplitude in AF patients.
What is the effect of electrical remodelling in mouse atrial cardiomyocytes?
You see reduction of CaT amplitude and also contractile dysfunction measured by cell shortening.
What is the effect of metabolic remodelling: mitochondrial damage and oxidative stress
What are the major roles of NAD(H) in cellular physiology?
NAD as co-substrate -->> cellular signalling
What induces Tachypacing (TP)
Tachypacing (TP) induced PARP activation in HL-1 cardiomyocytes for AF
We checked the activity of PARP in the cellular model of AF by staining the polyADPribosylated protein (PAR) with fluorescence. We saw significantly increase of the P
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