Cardiovascular research · 2025
Vascular regenerative deficiencies in people with elevated lipoprotein(a): the Lp(a)-VRCE CardioLink-16 translational study.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Moroney Michael, Casey Jack H, Teoh Hwee, Krishnaraj Aishwarya, Pan Yi, Quan Adrian, Patel Shubh K, Dennis Fallon, He Arianna Z, Park Brady, Verma Raj, Misner Elizabeth, Seguchi Ryuta, Hassan Syed M Ali, Dennis Cole J, Meglis Gus, Pandey Ambarish, Butler Javed, Mazer Cyril David, Byrne Robert A, Koschinsky Marlys L, Hess David A, Verma Subodh
Аннотация
AIMS: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD); however, the relationship between Lp(a) and the capacity for vascular repair remains unclear. Depletion of vascular regenerative (VR) progenitor cells has been shown to be a novel indicator of compromised vascular repair in people living with cardiometabolic disorders. The purpose of this study was to determine if elevated levels of Lp(a) modify VR cell content properties.
METHODS AND RESULTS: The cross-sectional, multi-site Lipoprotein(a) and Vascular Regenerative Cell Content CardioLink-16 [Lp(a)-VRCE] study enrolled 40 individuals-20 with Lp(a) ≥100 nmol/L and 20 with Lp(a) <100 nmol/L. Isolated peripheral blood mononuclear cells were analysed by multi-parameter flow cytometry. VR progenitor cells were identified based on high aldehyde dehydrogenase (ALDH) activity, in combination with primitive vs. mature lineage-specific cell surface markers. The Lp(a) ≥100 nmol/L group exhibited baseline characteristic differences compared with the Lp(a) <100 nmol/L group such as lower estimated glomerular filtration rate (86.9 vs. 100.1 mL/min/1.73 m2), lower total cholesterol (4.0 vs. 4.8 mmol/L), greater statin use (90 vs. 60%), and a higher prevalence of ASCVD (60 vs. 25%). The Lp(a) ≥100 nmol/L group had lower frequencies of pro-angiogenic ALDHhiSSClowCD133+ (P = 0.0008) and ALDHhiSSClowCD34+CD133+ (P = 0.005) progenitor cells with pro-angiogenic secretory function. Compared with those in the Lp(a) <100 nmol/L group, individuals in the Lp(a) ≥100 nmol/L group demonstrated a higher frequency of M1-polarized pro-inflammatory monocytes (ALDHhiSSCmidCD86+CD163-; P = 0.007) and a lower frequency of ALDHhiSSChiCD49d+ granulocyte precursor cells (P = 0.04) that are involved in vessel repair.
CONCLUSION: In this translational study, people with an Lp(a) ≥100 nmol/L had fewer VR cells and more pro-inflammatory polarized monocyte precursor cells than those with Lp(a) levels <100 nmol/L. These findings suggest that vessel repair activities may be compromised in individuals with elevated Lp(a) levels.
REGISTRATION: Lp(a)-VRCE ClinicalTrials.gov: NCT06626659.
METHODS AND RESULTS: The cross-sectional, multi-site Lipoprotein(a) and Vascular Regenerative Cell Content CardioLink-16 [Lp(a)-VRCE] study enrolled 40 individuals-20 with Lp(a) ≥100 nmol/L and 20 with Lp(a) <100 nmol/L. Isolated peripheral blood mononuclear cells were analysed by multi-parameter flow cytometry. VR progenitor cells were identified based on high aldehyde dehydrogenase (ALDH) activity, in combination with primitive vs. mature lineage-specific cell surface markers. The Lp(a) ≥100 nmol/L group exhibited baseline characteristic differences compared with the Lp(a) <100 nmol/L group such as lower estimated glomerular filtration rate (86.9 vs. 100.1 mL/min/1.73 m2), lower total cholesterol (4.0 vs. 4.8 mmol/L), greater statin use (90 vs. 60%), and a higher prevalence of ASCVD (60 vs. 25%). The Lp(a) ≥100 nmol/L group had lower frequencies of pro-angiogenic ALDHhiSSClowCD133+ (P = 0.0008) and ALDHhiSSClowCD34+CD133+ (P = 0.005) progenitor cells with pro-angiogenic secretory function. Compared with those in the Lp(a) <100 nmol/L group, individuals in the Lp(a) ≥100 nmol/L group demonstrated a higher frequency of M1-polarized pro-inflammatory monocytes (ALDHhiSSCmidCD86+CD163-; P = 0.007) and a lower frequency of ALDHhiSSChiCD49d+ granulocyte precursor cells (P = 0.04) that are involved in vessel repair.
CONCLUSION: In this translational study, people with an Lp(a) ≥100 nmol/L had fewer VR cells and more pro-inflammatory polarized monocyte precursor cells than those with Lp(a) levels <100 nmol/L. These findings suggest that vessel repair activities may be compromised in individuals with elevated Lp(a) levels.
REGISTRATION: Lp(a)-VRCE ClinicalTrials.gov: NCT06626659.