Lecture 5- therapeutic angiogenesis Flashcards

1
Q

what is the principle cause of death in the world

A

CVD (50%)

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2
Q

what is the major cause of CVD

A

atherosclerosis

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3
Q

what are the non-modifiable risk factors for CVD

A

Age Sex (male) family history

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4
Q

what are the modifiable risk factors for CVD

A

smoking, hypertension, diabetes, obesity, high cholesterol

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5
Q

what are the clinical manifestations of CVD

A

chronic, angina, heart attack, stroke, peripheral arterial disease (PAD)

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6
Q

how is narrowing of blood vessels visualised

A

angiogram

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7
Q

what are the symptoms of PAD

A

initially long distance claudication (difficulty walking long distances) limited functionality, chronic pain, ulcers and gangrene

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8
Q

once a foot ulcer occurs in PAD, what is the outlook for the patient

A

50% chance of being alive with 2 legs in a years time and 30% chance of survival after 5 years

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9
Q

how is PAD diagnosed

A

history, examination, ankle-brachial bp index, angiogram

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10
Q

what are the surgical methods for treating PAD

A

endovascular treatments using catheters and balloons, open surgery to clear out blood vessels, bypass and finally amputation

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11
Q

how can therapeutic angiogenesis used to treat PAD

A

administration of pro-angiogenic growth factors to stimulate proliferation of blood vessels and improve perfusion

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12
Q

how are growth factors delivered for angiogenic therapy

A

they can be injected into cells via plasmids or viruses or directly injected into arteries

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13
Q

what have been the results using IMVEGF-A gene therapy

A

positive showing wider blood vessels and healing ulcers

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14
Q

what have been the results of FGF-1 gene therapy

A

no significant difference in 2nd or 3rd stage clinical trials- may need higher doses or to be taken longer or perhaps a single growth factor is not sufficient

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15
Q

what have been the results of hepatocyte growth factor gene therapy trials

A

phase 2 clinical trial very successful so should begin phase 3 soon

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16
Q

what are the concerns using angiogenic gene therapy

A

could exacerbate diseases such as cancer or diabetic retinopathy, virus use, arrhythmia due to new vessels and no current proof that it works

17
Q

how have stem cells been used to treat PAD

A

induce paracrine and growth factor mediation to promote angiogenesis. TACT study has had positive results on human trials however PROVASA study showed no significance- mixed results

18
Q

what are the potential future treatments for PAD

A

recombinant cytokines, gene therapy, stem cell therapy

19
Q

what are the challenges posed in designing new therapies to treat PAD

A

timing, mode of delivery and dose as well as the fact promotion of angiogenesis appears to cause diseased blood vessels to worsen. finally need to be able to do cell tracking in vivo to monitor where the medicine is going