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UNIT M3
CHIEF:PROFESSOR DR.SATHISHKUMAR
MBBS,MD
ASSISTSNT PROFESSORS:
DR.MUTHUMANI
MBBS,DA,MD,MRCP(UK)
MICROPLASTICS AND NANOPLASTICS IN
ATHEROMAS AND CARDIOVASCULAR EVENTS
ABSTRACT
BACKGROUND:
Microplastics and nanoplastics(MNPs) are emerging as a potential risk
factor for cardiovascular disease in preclinical studies
METHODS:
A prospective ,multicenter,observational study involving patients who
were undergoing carotid endarterectomy for asymptomatic carotid
artery disease
The excised carotid plaque specimens were analyzed for the presence
of MNPs with the use of pyrolysis –gas chromatography-mass
spectrometry,stable isotope analysis and electron microscopy
Inflammatory biomarkers were assessed with ELISA and
immunohistochemical assay
The primary end point was a composite of MI,stroke,or death from any
cause among patients who had evidence of MNPs in plaque as
compared with patients with plaque that showed no evidence of MNPs
RESULTS:
Patients in whom MNPs were detected within the atheroma were at
higher risk for a primary end point than those in whom these substances
were not detected
INTRODUCTION
• Plastics can pollute the environment by way of ocean currents,atmospheric
winds and terrestrial phenomena.
• Once released into nature,plastics are susceptible to degrations,leading to
a formation of microplastics(particles less than 5mm)and nanoplastics
(plastics smaller than 1000nm)
• Several studies show that MNPs enter the human body through
ingestion,inhalation and skin exposure
• MNPs have been found in placenta,lungs,liver as well as in breast
milk,urine and blood
• Recent studies performed in preclinical models have led to suggestion
of MNPs as s new risk factor for cardiovascular diseases
• Data from invitro studies suggest that specific MNPs promote
oxidative stress,inflammation,and apoptosis in endothelial and
vascular cells
PATIENTS
ELIGIBILITY CRITERIA:
Age 18 to 75 yrs
Asympatomatic extracranial high grade(>70%)ICA stenois
Scheduled to undergo carotid endarterectomy
EXCLUSION CRITERIA:
Evidence of heart failure,valvular defcts,
Malignant neoplasms
Lost during follow up
END POINTS
PRIMARY END POINT
Non fatal MI, stroke or death from any cause among patients with
plaque containing MNPs and patient with plaque without MNPs
SECONDARY END POINT
Tissue biomarkers IL-18,IL-1 beta,TNF alpha,IL-6,CD68,CD3 and
collagen in patient with MNPs compared to those without MNPs
 Of the 257 patients who
completed a mean (+/-SD)
follow-up of 33.7+-6.9
months,150 (58.4%) had a
detectable amount of
polyethylene in excised carotid
plaque and 31 of those(12.1%)
had a measurable amount of
polyvinyl chloride in the carotid
plaque
 Mean level of polyethylene was
21.7+/-24.5microgram per mg of
plaque
 Mean level of polyvinyl chloride
was 5.2+/-2.4microgram per mg
ELECTRON MICROSCOPY AND ANALYSIS WITH STABLE
ISOTOPES:
To substantiate the results obtained with pyrolysis-gas
chromatography-mass spectrometry and to gain preliminary
information about the size of MNP particles
Plaque samples that were positive for both polyethylene and polyvinyl
chloride from 10 randomly selected patients using transmission
electron microscopy and scanning electron microscopy
EM showed the presence of particles with jagged edges that were
probably of foreign origin within the foamy macrophages present in
atheromatous plaque and in the amorphous material of plaque
Stable isotope analysis was performed on 26 random patient plaque
samples because petroleum-derived plastics have lower the ratio of
carbon -13 to carbon-12 than human tissues.
This analysis identified two distinct clusters of patients-one group with
higher values and with lower ratios,respectively,of carbon-13 to
carbon-12.
Lower isotopic values could be due to contamination with MNPs,since
petroleum derived material has an isotopic signal lower than that of
human tissues
Lower isotopic values were more evident in plaque that had evidence
of MNPs
PLAQUE PHENOTYPE
MNPs can induce proinflammatory pathways,four inflammatory
markers were measured with ELISA
INTERLEUKIN-18
INTERLEUKIN-1 BETA
INTERLEUKIN-6
TNF-ALPHA
Collagen content of plaque samples and levels of CD3 and CD68,two
markers of lymphocyte and macrophage infiltration respectively
assessed by means of IHC assay
CARDIOVASCULAR EVENTS
The primary end point event(nonfatal MI,nonfatal stroke,or death from
any cause)occurred in 8 of 107 patients that did not have MNPs(2.2
events per100 patient years) and in 30 of 150 patients (20%) that had
evidence of MNPs at 33.7+/-6.9 months.
Patients with MNPs in plaque had a higher risk of having primary end
point event than patients with no evidence of MNPs(hazard
ratio,4.53;95%CI);P<0.001
DISCUSSION
• Among patients with asymptomatic high grade (>70%)carotid artery
stenosis who were undergoing carotid endarterectomy,those with
evidence of MNPs had a greater incidence of MI,stroke or death
• Observational data from occupational exposure studies suggest an
increased risk of cardiovascular disease among persons who are
exposed to plastics related pollution
• According to a WHO statement,MNPs larger than 150 or 10
micrometer in diameter are not absorbed into blood and do not
penetrate blood vessels
• Data from studies in humans have shown that MNPs of up to
30micrometer in size have been detected in liver samples,upto
10micrometer in placenta samples,upto 88micrometer in lung
samples,upto 12 to 75micrometer in breast milk and urine,and more
than 700nm in whole blood
• Other studies have suggested that polyethylene and polyvinyl chloride
were also the most abundant MNPs found in human breast milk and
urine
• Polyethylene and polyvinyl chloride ,in there various forms are used in
a wide range of applications ,including production of
food,cosmetics,containers and water pipes
• MNPs have been found in drinking water,and air also in a form bound
to fine,inhalable particulate matter witg an diameter of 2.5 micrometer
or less
• Cannot establish why only polyethylene and polyvinyl chloride among
the 11 types of plastics assessed,were detected
LIMITATIONS
• Do not prove casuality
• Did not consider levels of exposure to PM25 and PM10
• Laboratory contamination
• No socioeconomic data
• Findings not a representative of general population
• Did not explore the varoables of food and drinking water
• However ,results of our study shown that patients with MNPs that wee
detected in carotid artery plaque have a higher risk of composite end point of
MI,stroke ,or death from any cause at 34 months of follow up
THANK YOU

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microprocessor sand microphone emission role

  • 1. UNIT M3 CHIEF:PROFESSOR DR.SATHISHKUMAR MBBS,MD ASSISTSNT PROFESSORS: DR.MUTHUMANI MBBS,DA,MD,MRCP(UK) MICROPLASTICS AND NANOPLASTICS IN ATHEROMAS AND CARDIOVASCULAR EVENTS
  • 2.
  • 3. ABSTRACT BACKGROUND: Microplastics and nanoplastics(MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies METHODS: A prospective ,multicenter,observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis –gas chromatography-mass spectrometry,stable isotope analysis and electron microscopy
  • 4. Inflammatory biomarkers were assessed with ELISA and immunohistochemical assay The primary end point was a composite of MI,stroke,or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs RESULTS: Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end point than those in whom these substances were not detected
  • 5. INTRODUCTION • Plastics can pollute the environment by way of ocean currents,atmospheric winds and terrestrial phenomena. • Once released into nature,plastics are susceptible to degrations,leading to a formation of microplastics(particles less than 5mm)and nanoplastics (plastics smaller than 1000nm) • Several studies show that MNPs enter the human body through ingestion,inhalation and skin exposure • MNPs have been found in placenta,lungs,liver as well as in breast milk,urine and blood
  • 6. • Recent studies performed in preclinical models have led to suggestion of MNPs as s new risk factor for cardiovascular diseases • Data from invitro studies suggest that specific MNPs promote oxidative stress,inflammation,and apoptosis in endothelial and vascular cells
  • 7.
  • 8. PATIENTS ELIGIBILITY CRITERIA: Age 18 to 75 yrs Asympatomatic extracranial high grade(>70%)ICA stenois Scheduled to undergo carotid endarterectomy EXCLUSION CRITERIA: Evidence of heart failure,valvular defcts, Malignant neoplasms Lost during follow up
  • 9. END POINTS PRIMARY END POINT Non fatal MI, stroke or death from any cause among patients with plaque containing MNPs and patient with plaque without MNPs SECONDARY END POINT Tissue biomarkers IL-18,IL-1 beta,TNF alpha,IL-6,CD68,CD3 and collagen in patient with MNPs compared to those without MNPs
  • 10.  Of the 257 patients who completed a mean (+/-SD) follow-up of 33.7+-6.9 months,150 (58.4%) had a detectable amount of polyethylene in excised carotid plaque and 31 of those(12.1%) had a measurable amount of polyvinyl chloride in the carotid plaque  Mean level of polyethylene was 21.7+/-24.5microgram per mg of plaque  Mean level of polyvinyl chloride was 5.2+/-2.4microgram per mg
  • 11.
  • 12. ELECTRON MICROSCOPY AND ANALYSIS WITH STABLE ISOTOPES: To substantiate the results obtained with pyrolysis-gas chromatography-mass spectrometry and to gain preliminary information about the size of MNP particles Plaque samples that were positive for both polyethylene and polyvinyl chloride from 10 randomly selected patients using transmission electron microscopy and scanning electron microscopy EM showed the presence of particles with jagged edges that were probably of foreign origin within the foamy macrophages present in atheromatous plaque and in the amorphous material of plaque
  • 13. Stable isotope analysis was performed on 26 random patient plaque samples because petroleum-derived plastics have lower the ratio of carbon -13 to carbon-12 than human tissues. This analysis identified two distinct clusters of patients-one group with higher values and with lower ratios,respectively,of carbon-13 to carbon-12. Lower isotopic values could be due to contamination with MNPs,since petroleum derived material has an isotopic signal lower than that of human tissues Lower isotopic values were more evident in plaque that had evidence of MNPs
  • 14.
  • 15. PLAQUE PHENOTYPE MNPs can induce proinflammatory pathways,four inflammatory markers were measured with ELISA INTERLEUKIN-18 INTERLEUKIN-1 BETA INTERLEUKIN-6 TNF-ALPHA Collagen content of plaque samples and levels of CD3 and CD68,two markers of lymphocyte and macrophage infiltration respectively assessed by means of IHC assay
  • 16.
  • 17.
  • 18. CARDIOVASCULAR EVENTS The primary end point event(nonfatal MI,nonfatal stroke,or death from any cause)occurred in 8 of 107 patients that did not have MNPs(2.2 events per100 patient years) and in 30 of 150 patients (20%) that had evidence of MNPs at 33.7+/-6.9 months. Patients with MNPs in plaque had a higher risk of having primary end point event than patients with no evidence of MNPs(hazard ratio,4.53;95%CI);P<0.001
  • 19.
  • 20. DISCUSSION • Among patients with asymptomatic high grade (>70%)carotid artery stenosis who were undergoing carotid endarterectomy,those with evidence of MNPs had a greater incidence of MI,stroke or death • Observational data from occupational exposure studies suggest an increased risk of cardiovascular disease among persons who are exposed to plastics related pollution • According to a WHO statement,MNPs larger than 150 or 10 micrometer in diameter are not absorbed into blood and do not penetrate blood vessels
  • 21. • Data from studies in humans have shown that MNPs of up to 30micrometer in size have been detected in liver samples,upto 10micrometer in placenta samples,upto 88micrometer in lung samples,upto 12 to 75micrometer in breast milk and urine,and more than 700nm in whole blood • Other studies have suggested that polyethylene and polyvinyl chloride were also the most abundant MNPs found in human breast milk and urine
  • 22. • Polyethylene and polyvinyl chloride ,in there various forms are used in a wide range of applications ,including production of food,cosmetics,containers and water pipes • MNPs have been found in drinking water,and air also in a form bound to fine,inhalable particulate matter witg an diameter of 2.5 micrometer or less • Cannot establish why only polyethylene and polyvinyl chloride among the 11 types of plastics assessed,were detected
  • 23. LIMITATIONS • Do not prove casuality • Did not consider levels of exposure to PM25 and PM10 • Laboratory contamination • No socioeconomic data • Findings not a representative of general population • Did not explore the varoables of food and drinking water • However ,results of our study shown that patients with MNPs that wee detected in carotid artery plaque have a higher risk of composite end point of MI,stroke ,or death from any cause at 34 months of follow up