Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins

Ravinder Sodi; Jarlath Eastwood; Muriel Caslake; Chris J Packard; Laura Denby

doi:10.1016/j.cca.2016.12.031

Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins

Ravinder Sodi, Jarlath Eastwood, Muriel Caslake, Chris J Packard, Laura Denby

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background: Small non-coding microRNAs (miR) have important regulatory roles
and are used as biomarkers of disease. We investigated the relationship between
lipoproteins and circulating miR-30c, evaluated how they are transported in
circulation and determined whether statins altered the circulating concentration of miR-30c.
Methods: To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated. Ultracentrifugation and nanoparticle tracking analysis was used to evaluate the transportation of miR-30c in the circulation by lipoproteins and extracellular vesicles in three healthy volunteers. Using archived samples from previous studies, the effects of 40 mg rosuvastatin (n = 22) and 40 mg pravastatin (n = 24) on miR-30c expression was also examined. RNA extraction, reverse transcriptionquantitative real-time polymerase chain reaction was carried out using standard procedures.

Results: When stratified according to total cholesterol concentration, there was
increased miR-30c expression in the highest compared to the lowest tertile (p=0.035). There was significant positive correlation between miR-30c and total- (r=0.367; p= 0.002) and LDL-cholesterol (r=0.391; p=0.001). We found that miR-30c was transported in both exosomes and on HDL3. There was a 3.8-fold increased expression of circulating miR-30c after pravastatin treatment for 1-y (p=0.005) but no significant change with atorvastatin after 8-weeks (p=0.145).

Conclusions: This study shows for the first-time in humans that circulating miR-30c is significantly, positively correlated with total- and LDL-cholesterol implicating regulatory functions in lipid homeostasis. We show miR-30c is transported in both exosomes and on HDL3 and pravastatin therapy significantly increased circulating 4 miR-30c expression adding to the pleiotropic dimensions of statins.

Original language	English
Pages (from-to)	13-19
Journal	Clinica Chimica Acta
Volume	466
Early online date	3 Jan 2017
DOIs	https://doi.org/10.1016/j.cca.2016.12.031
Publication status	Published - Mar 2017

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10.1016/j.cca.2016.12.031

Denby Jan 2017
This is the authors accepted manuscript as accepted by Clin Chim Acta on the 30/12/16
Accepted author manuscript, 225 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Laura Denby
- laura.denbyed.acuk
- Deanery of Clinical Sciences - Senior Lecturer
- Centre for Cardiovascular Science
Person: Academic: Research Active

Cite this

@article{af1fd8c7b81246ed9a0d4f1e29c8f42e,

title = "Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins",

abstract = "Background: Small non-coding microRNAs (miR) have important regulatory rolesand are used as biomarkers of disease. We investigated the relationship betweenlipoproteins and circulating miR-30c, evaluated how they are transported incirculation and determined whether statins altered the circulating concentration of miR-30c.Methods: To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated. Ultracentrifugation and nanoparticle tracking analysis was used to evaluate the transportation of miR-30c in the circulation by lipoproteins and extracellular vesicles in three healthy volunteers. Using archived samples from previous studies, the effects of 40 mg rosuvastatin (n = 22) and 40 mg pravastatin (n = 24) on miR-30c expression was also examined. RNA extraction, reverse transcriptionquantitative real-time polymerase chain reaction was carried out using standard procedures.Results: When stratified according to total cholesterol concentration, there wasincreased miR-30c expression in the highest compared to the lowest tertile (p=0.035). There was significant positive correlation between miR-30c and total- (r=0.367; p= 0.002) and LDL-cholesterol (r=0.391; p=0.001). We found that miR-30c was transported in both exosomes and on HDL3. There was a 3.8-fold increased expression of circulating miR-30c after pravastatin treatment for 1-y (p=0.005) but no significant change with atorvastatin after 8-weeks (p=0.145).Conclusions: This study shows for the first-time in humans that circulating miR-30c is significantly, positively correlated with total- and LDL-cholesterol implicating regulatory functions in lipid homeostasis. We show miR-30c is transported in both exosomes and on HDL3 and pravastatin therapy significantly increased circulating 4 miR-30c expression adding to the pleiotropic dimensions of statins.",

author = "Ravinder Sodi and Jarlath Eastwood and Muriel Caslake and Packard, {Chris J} and Laura Denby",

note = "Contributions - All authors have: i) made a substantial contribution to the concept and design, acquisition of data or analysis and interpretation of data; ii) drafted the article or revised it critically for important intellectual content; iii) approved the version to be published. Research Funding: LD is in receipt of a Kidney Research UK fellowship PD6/2012 and has a PhD studentship co-sponsored by Regulus Therapeutics. Part of this work was funded by Medical Research Scotland Scholarship to JE. Authors{\textquoteright} Disclosures or Potential Conflicts of Interest - Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Expert Testimony: None declared. Role of Sponsor: The funding organizations played no role in the design of the study, review and interpretation of data, or preparation or approval of manuscript. Acknowledgements: We acknowledge the technical assistance of Josephine Clooney and James Philip Stewart, Institute of Cardiovascular and Medical Sciences, University of Glasgow. We thank the West of Scotland Coronary Prevention Study (WOSCOPS) committee and Astra Zeneca for providing samples from their respective study cohorts.",

year = "2017",

month = mar,

doi = "10.1016/j.cca.2016.12.031",

language = "English",

volume = "466",

pages = "13--19",

journal = "Clinica Chimica Acta",

issn = "0009-8981",

publisher = "Elsevier",

}

TY - JOUR

T1 - Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins

AU - Sodi, Ravinder

AU - Eastwood, Jarlath

AU - Caslake, Muriel

AU - Packard, Chris J

AU - Denby, Laura

N1 - Contributions - All authors have: i) made a substantial contribution to the concept and design, acquisition of data or analysis and interpretation of data; ii) drafted the article or revised it critically for important intellectual content; iii) approved the version to be published. Research Funding: LD is in receipt of a Kidney Research UK fellowship PD6/2012 and has a PhD studentship co-sponsored by Regulus Therapeutics. Part of this work was funded by Medical Research Scotland Scholarship to JE. Authors’ Disclosures or Potential Conflicts of Interest - Employment or Leadership: None declared. Consultant or Advisory Role: None declared. Stock Ownership: None declared. Honoraria: None declared. Expert Testimony: None declared. Role of Sponsor: The funding organizations played no role in the design of the study, review and interpretation of data, or preparation or approval of manuscript. Acknowledgements: We acknowledge the technical assistance of Josephine Clooney and James Philip Stewart, Institute of Cardiovascular and Medical Sciences, University of Glasgow. We thank the West of Scotland Coronary Prevention Study (WOSCOPS) committee and Astra Zeneca for providing samples from their respective study cohorts.

PY - 2017/3

Y1 - 2017/3

N2 - Background: Small non-coding microRNAs (miR) have important regulatory rolesand are used as biomarkers of disease. We investigated the relationship betweenlipoproteins and circulating miR-30c, evaluated how they are transported incirculation and determined whether statins altered the circulating concentration of miR-30c.Methods: To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated. Ultracentrifugation and nanoparticle tracking analysis was used to evaluate the transportation of miR-30c in the circulation by lipoproteins and extracellular vesicles in three healthy volunteers. Using archived samples from previous studies, the effects of 40 mg rosuvastatin (n = 22) and 40 mg pravastatin (n = 24) on miR-30c expression was also examined. RNA extraction, reverse transcriptionquantitative real-time polymerase chain reaction was carried out using standard procedures.Results: When stratified according to total cholesterol concentration, there wasincreased miR-30c expression in the highest compared to the lowest tertile (p=0.035). There was significant positive correlation between miR-30c and total- (r=0.367; p= 0.002) and LDL-cholesterol (r=0.391; p=0.001). We found that miR-30c was transported in both exosomes and on HDL3. There was a 3.8-fold increased expression of circulating miR-30c after pravastatin treatment for 1-y (p=0.005) but no significant change with atorvastatin after 8-weeks (p=0.145).Conclusions: This study shows for the first-time in humans that circulating miR-30c is significantly, positively correlated with total- and LDL-cholesterol implicating regulatory functions in lipid homeostasis. We show miR-30c is transported in both exosomes and on HDL3 and pravastatin therapy significantly increased circulating 4 miR-30c expression adding to the pleiotropic dimensions of statins.

AB - Background: Small non-coding microRNAs (miR) have important regulatory rolesand are used as biomarkers of disease. We investigated the relationship betweenlipoproteins and circulating miR-30c, evaluated how they are transported incirculation and determined whether statins altered the circulating concentration of miR-30c.Methods: To determine the relationship between lipoproteins and circulating miR-30c, serum samples from 79 subjects recruited from a lipid clinic were evaluated. Ultracentrifugation and nanoparticle tracking analysis was used to evaluate the transportation of miR-30c in the circulation by lipoproteins and extracellular vesicles in three healthy volunteers. Using archived samples from previous studies, the effects of 40 mg rosuvastatin (n = 22) and 40 mg pravastatin (n = 24) on miR-30c expression was also examined. RNA extraction, reverse transcriptionquantitative real-time polymerase chain reaction was carried out using standard procedures.Results: When stratified according to total cholesterol concentration, there wasincreased miR-30c expression in the highest compared to the lowest tertile (p=0.035). There was significant positive correlation between miR-30c and total- (r=0.367; p= 0.002) and LDL-cholesterol (r=0.391; p=0.001). We found that miR-30c was transported in both exosomes and on HDL3. There was a 3.8-fold increased expression of circulating miR-30c after pravastatin treatment for 1-y (p=0.005) but no significant change with atorvastatin after 8-weeks (p=0.145).Conclusions: This study shows for the first-time in humans that circulating miR-30c is significantly, positively correlated with total- and LDL-cholesterol implicating regulatory functions in lipid homeostasis. We show miR-30c is transported in both exosomes and on HDL3 and pravastatin therapy significantly increased circulating 4 miR-30c expression adding to the pleiotropic dimensions of statins.

U2 - 10.1016/j.cca.2016.12.031

DO - 10.1016/j.cca.2016.12.031

M3 - Article

SN - 0009-8981

VL - 466

SP - 13

EP - 19

JO - Clinica Chimica Acta

JF - Clinica Chimica Acta

ER -

Relationship between circulating microRNA-30c with total- and LDL-cholesterol, their circulatory transportation and effect of statins

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