Endothelial Progenitor Cells May Be Related to Major Amputation after Angioplasty in Patients with Critical Limb Ischemia.

BACKGROUND: Critical limb ischemia represents an advanced stage of peripheral arterial disease. Angioplasty improves blood flow to the limb; however, some patients progress irreversibly to lower limb amputation. Few studies have explored the predictive potential of biomarkers during postangioplasty outcomes. AIM: To evaluate the behavior of endothelial progenitor cells in patients with critical limb ischemia, in relation to their postangioplasty outcome. METHODS: Twenty patients with critical limb ischemia, candidates for angioplasty, were enrolled. Flow-mediated dilation, as well as endothelial progenitor cells (subpopulations CD45+/CD34+/CD133+/CD184+ and CD45+/CD/34+/KDR[VEGFR-2]+ estimated by flow cytometry) from blood flow close to vascular damage, were evaluated before and after angioplasty. Association with lower limb amputation during a 30-day follow-up was analyzed. RESULTS: Endothelial progenitor cells were related with flow-mediated dilation. A higher number of baseline EPCs CD45+CD34+KDR+, as well as an impaired reactivity of endothelial progenitor cells CD45+CD34+CD133+CD184+ after angioplasty, were observed in cases further undergoing major limb amputation, with a significant discrimination ability and risk (0.75, specificity 0.83 and RR 4.5 p < 0.05). CONCLUSIONS: Endothelial progenitor cells were related with endothelial dysfunction, whereas a higher baseline number of the subpopulation CD45+CD34+KDR+, as well as an impaired reactivity of subpopulation CD45+CD34+CD133+CD184+ after angioplasty, showed a predictive ability for major limb amputation in patients with critical limb ischemia.

Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity.

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) represents an advanced stage of the peripheral arterial disease. Angioplasty improves the blood flow to the lower limb; however, some patients irreversibly progress to limb amputation. The extent of vascular damage and the mechanisms of vascular repair are factors affecting post-angioplasty outcome. Mononuclear Progenitor Cells (MPCs) are reactive to vascular damage and repair, with the ability to reflect vascular diseases. The present protocol describes quantification of MPCs obtained from blood circulation from vessel close to the angioplasty site, as well as its relationship with endothelial dysfunction and its predictive ability for limb amputation in the next 30 days after angioplasty in patients with CLI.

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty.

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.

Coronary circulating mononuclear progenitor cells and soluble biomarkers in the cardiovascular prognosis after coronary angioplasty.

Currently, there are no confident prognostic markers in patients with coronary artery disease (CAD) undergoing angioplasty. The present study aimed to explore whether basal coronary circulating Mononuclear Progenitor Cells (MPCs) and vascular injury biomarkers were related to development of major adverse cardiovascular events (MACEs) and may impact clinical prognosis. METHODS: The number of MPCs and soluble mediators such as IL-1ß, sICAM-1, MMP-9, malondialdehyde, superoxide dismutase and nitric oxide were determined in coronary and peripheral circulation. Prognostic ability for MACEs occurring at 6 months follow up was assessed by time-to-event and event free survival estimations. RESULTS: Lower coronary circulating MPCs subpopulations CD45+ CD34+ , CD45+ CD34+ CD133+ CD184+ , lower MMP-9 and higher sICAM-1 significantly associated with MACEs presentation and showed prognostic ability; while peripheral blood increase in malondialdehyde and decreased superoxide dismutase were observed in patients with MACEs. CONCLUSION: Coronary concentration of biomarkers related with vascular repair, such as MPCs subpopulations and adhesion molecules, may predict MACEs and impact prognosis in patients with CAD undergoing angioplasty; whereas peripheral pro-oxidative condition may be also associated.