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Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome.

Dessapt-Baradez C, Reza M, Sivakumar G, Hernandez-Fuentes M, Markakis K, Gnudi L, Karalliedde J - PLoS ONE (2011)

Bottom Line: Brachial systolic and pulse pressures were similar.VPC number/function and arterial stiffness or BP measures were not correlated.Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Division at Guy's and St Thomas and King's College Hospitals, King's College London, London, United Kingdom. cecile.dessapt@kcl.ac.uk

ABSTRACT

Objective: Subjects with Polycystic ovarian syndrome (PCOS) are at increased risk of Type 2 diabetes mellitus (T2DM). The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC) are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness predict cardio-metabolic disease in at-risk populations.

Design: We studied VPC and arterial stiffness measures in non-obese PCOS subjects as compared to age and body mass index (BMI) matched healthy controls in a cross-sectional study.

Methods: Fourteen subjects with PCOS and 12 controls of similar age, BMI (all <30 kg/m(2)) and metabolic profile were studied. VPC number and in vitro function were studied by flow cytometry and tube formation assays respectively. Augmentation index (AIx), a measure of central arterial stiffness, and central (aortic) blood pressures (BP) were measured by applanation tonometry.

Results: Subjects with PCOS had a reduced number, mean±SEM, of circulating CD34(+)133(+) VPCs (317.5±51.0 vs. 558.3±101.2, p = 0.03) and impaired in vitro tube formation (completed tube area 1.0±0.06 vs. 1.2±0.05×10(6) µm(2) p = 0.02). PCOS subjects had significantly higher AIx (18.4±1.9% vs. 4.9±2.0%) and this difference remained significant even after adjustments for age, BMI and smoking (p = 0.003) in multivariate analyses. Central systolic and pulse pressure were higher in PCOS subjects but these differences were not statistically significant after adjustment for age. Brachial systolic and pulse pressures were similar. VPC number/function and arterial stiffness or BP measures were not correlated.

Conclusions: Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness. These changes in novel vascular risk markers may explain the enhanced risk of T2DM and CVD in PCOS.

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Related in: MedlinePlus

Tubule formation assay in healthy controls (A) and PCOS (B) patients.Panels A and B are representative pictures of the tubule network formed by the VPC (white dots) and HUVECs. The white line represents the surface area which was measured i.e. area formed by complete closed tubes.
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pone-0020317-g002: Tubule formation assay in healthy controls (A) and PCOS (B) patients.Panels A and B are representative pictures of the tubule network formed by the VPC (white dots) and HUVECs. The white line represents the surface area which was measured i.e. area formed by complete closed tubes.

Mentions: Subjects with PCOS had a significantly lower number of circulating CD34+133+ VPC, 317.5±51.0 vs. 558.3±101.2, per 106 lymphomonocyte events p = 0.03 (Figure 1a). PCOS subjects also had lower number CD34+ cells (697.5±114.5 vs. 929.9±149.3p = 0.2). CD34+CD133+KDR+ and CD34+KDR+ cells per 106 lymphomonocyte events were very small in both groups with no statistically significant differences noted between PCOS subjects and healthy controls. Age and smoking status were not significantly associated with CD34+CD133+ VPC number in univariate correlation analyses (Table 2). VPC functional assays were performed in 10 PCOS and 8 control consecutive patients from the population described comparable for all characteristics. The phenotype of VPC cultured for 7 days and 14 days did not differ between the groups however day 14 VPC were characterised by greater expression of endothelial markers such as von Willebrand factor, CD31 and eNOS compared to day 7 VPC which expressed predominantly white cell markers such as CD14 as previously reported [11]. Migration and tube formation assays with VPC cultured for 7 days showed similar results in both groups (data not shown). VPC cultured for 14 days from PCOS subjects had less migration (22,553±589 vs. 25,062±1523) but this difference did not reach statistical significance (p = 0.23). However VPC cultured for 14 days from PCOS subjects showed a significantly reduced completed tube area (1.0±0.06 vs. 1.2±0.05×106 µm2 p = 0.02) with VEGF-A compared to controls (Figure 1b and Figure 2).


Circulating vascular progenitor cells and central arterial stiffness in polycystic ovary syndrome.

Dessapt-Baradez C, Reza M, Sivakumar G, Hernandez-Fuentes M, Markakis K, Gnudi L, Karalliedde J - PLoS ONE (2011)

Tubule formation assay in healthy controls (A) and PCOS (B) patients.Panels A and B are representative pictures of the tubule network formed by the VPC (white dots) and HUVECs. The white line represents the surface area which was measured i.e. area formed by complete closed tubes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105021&req=5

pone-0020317-g002: Tubule formation assay in healthy controls (A) and PCOS (B) patients.Panels A and B are representative pictures of the tubule network formed by the VPC (white dots) and HUVECs. The white line represents the surface area which was measured i.e. area formed by complete closed tubes.
Mentions: Subjects with PCOS had a significantly lower number of circulating CD34+133+ VPC, 317.5±51.0 vs. 558.3±101.2, per 106 lymphomonocyte events p = 0.03 (Figure 1a). PCOS subjects also had lower number CD34+ cells (697.5±114.5 vs. 929.9±149.3p = 0.2). CD34+CD133+KDR+ and CD34+KDR+ cells per 106 lymphomonocyte events were very small in both groups with no statistically significant differences noted between PCOS subjects and healthy controls. Age and smoking status were not significantly associated with CD34+CD133+ VPC number in univariate correlation analyses (Table 2). VPC functional assays were performed in 10 PCOS and 8 control consecutive patients from the population described comparable for all characteristics. The phenotype of VPC cultured for 7 days and 14 days did not differ between the groups however day 14 VPC were characterised by greater expression of endothelial markers such as von Willebrand factor, CD31 and eNOS compared to day 7 VPC which expressed predominantly white cell markers such as CD14 as previously reported [11]. Migration and tube formation assays with VPC cultured for 7 days showed similar results in both groups (data not shown). VPC cultured for 14 days from PCOS subjects had less migration (22,553±589 vs. 25,062±1523) but this difference did not reach statistical significance (p = 0.23). However VPC cultured for 14 days from PCOS subjects showed a significantly reduced completed tube area (1.0±0.06 vs. 1.2±0.05×106 µm2 p = 0.02) with VEGF-A compared to controls (Figure 1b and Figure 2).

Bottom Line: Brachial systolic and pulse pressures were similar.VPC number/function and arterial stiffness or BP measures were not correlated.Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Division at Guy's and St Thomas and King's College Hospitals, King's College London, London, United Kingdom. cecile.dessapt@kcl.ac.uk

ABSTRACT

Objective: Subjects with Polycystic ovarian syndrome (PCOS) are at increased risk of Type 2 diabetes mellitus (T2DM). The mechanism of this enhanced risk is unclear. Circulating vascular progenitor cells (VPC) are immature bone marrow derived cells capable of differentiating into mature endothelial cells. VPC number/function and central arterial stiffness predict cardio-metabolic disease in at-risk populations.

Design: We studied VPC and arterial stiffness measures in non-obese PCOS subjects as compared to age and body mass index (BMI) matched healthy controls in a cross-sectional study.

Methods: Fourteen subjects with PCOS and 12 controls of similar age, BMI (all <30 kg/m(2)) and metabolic profile were studied. VPC number and in vitro function were studied by flow cytometry and tube formation assays respectively. Augmentation index (AIx), a measure of central arterial stiffness, and central (aortic) blood pressures (BP) were measured by applanation tonometry.

Results: Subjects with PCOS had a reduced number, mean±SEM, of circulating CD34(+)133(+) VPCs (317.5±51.0 vs. 558.3±101.2, p = 0.03) and impaired in vitro tube formation (completed tube area 1.0±0.06 vs. 1.2±0.05×10(6) µm(2) p = 0.02). PCOS subjects had significantly higher AIx (18.4±1.9% vs. 4.9±2.0%) and this difference remained significant even after adjustments for age, BMI and smoking (p = 0.003) in multivariate analyses. Central systolic and pulse pressure were higher in PCOS subjects but these differences were not statistically significant after adjustment for age. Brachial systolic and pulse pressures were similar. VPC number/function and arterial stiffness or BP measures were not correlated.

Conclusions: Non-obese PCOS is characterized by a reduced VPC number, impaired VPC function and increased central arterial stiffness. These changes in novel vascular risk markers may explain the enhanced risk of T2DM and CVD in PCOS.

Show MeSH
Related in: MedlinePlus