Redox Biology Laboratory

Lab head: Dr Paul Witting
Location: Blackburn Building, Camperdown Campus

Protein modifications that potentially underlie the severity of acute myocardial infarct in hearts from diabetic rats. In addition, we have an established interest in monitoring oxidative stress in disease states including atherosclerosis, acute renal failure and cerebral ischemia injury (stroke).

Funding: ARC; National Heart Foundation; Diabetes Australia
Research approach equipment: Analytical Biochemistry: using analytical techniques such as liquid chromatography and liquid chromatography coupled with mass spectrometry, the redox biology lab assesses the mechanism of acute pathological processes. Molecular biology: we use quantitative gene analysis techniques to assess cellular and tissue response to experimental ischaemia reperfusion injury as a model for stroke and heart attack.

Characterizing experimental snore vibration damage to cultured human carotid artery endothelial cells as a precursor to carotid artery disease

Primary supervisor: Paul Witting

 

Obstructive sleep apnea (OSA) is amongst the most common chronic disorders of adults, with ~4% prevalence for middle aged men and ~2% for middle aged women (1), and is now regarded as an independent risk factor for cardiovascular disease. Early carotid atherosclerosis (increase in carotid intima-to-media thickness or cIMT) has been reported in OSA patients who were otherwise at low risk from classical risk factors. These data suggest linkage between OSAHS and carotid atherosclerosis, however, snoring was not measured and given its strong association with OSA, snoring was almost certainly present.

Snoring has been identified as a risk factor for chronic cardiovascular diseases including hypertension (2, 3), myocardial infarction (4), ischemic heart disease (6), and stroke (5). The increased relative risk (odds ratios) of stroke in habitual snorers is 1.26 - 2.13 (5,6,7). However, the role of snoring versus OSA is again unclear since they frequently co-exist and furthermore, snoring data are often derived from questionnaires rather than objective measurement.

We recently reported that endothelial dysfunction was evident in an animal model of snoring (8).  We will now use a unique in vitro cell-culture model, developed in our laboratory, in which cultured human carotid artery endothelial cells (HCEC) are exposed to snoring vibration energy at levels, frequencies, patterns and durations commensurate with those produced by human snorers. This methodology provides a bench assay for direct measurement of snoring vibration effects on HCEC function (e.g., reduced NO bioavailability). Dose response relationships will be established, gene expression patterns explored and a model created for probing mechanistic pathways and testing potential treatments (eg anti-oxidant therapies).

Techniques to be employed: cell culture, cell viability assays; isolation of mRNA and conversion to cDNA for gene analysis; assaying for NO production; intervention with ascorbic acid to prevent snore-induced damage.

References

  1. Young T et al. Occurrence of SDB in middle-aged adults. NEJM 328:1230-35,1993.
  2. Young T et al. Snoring as part of a dose-response relationship between SDB & blood pressure. Sleep 19(10 Suppl): S202-5, 1996.
  3. Mateika J et al. Snoring & arterial pressure during sleep. Am Rev Respir Dis 145:141-6, 1992.
  4. D’Alessandro R et al. Snoring as a risk factor for myocardial infarction BMJ 300:1557-8, 1990.
  5. Hu F et al. Snoring & cardiovascular disease in women. J Am Coll Cardiol 35:308-13, 2000.
  6. Jennum P et al. Snoring, stroke & ischaemic heart disease Int J Epidemiol 23:1159-64, 1994.
  7. Partinen M et al. Snoring & cerebral infarction. Lancet 326:1325-6, 1985.
  8. Cho JG, Witting PK, Verma M, Wu BJ, Shanu A, Kairaitis K, Amis TC, Wheatley JR. Tissue vibration induces carotid artery endothelial dysfunction: a mechanism linking snoring and carotid atherosclerosis? Sleep 34:751-757, 2011


Discipline: Pathology
Co-supervisors: Terry Amis
Keywords: Cardiovascular diseases, Inflammation, Biological and Medicinal Chemistry
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