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Bubb, K. J.

Publications and source records attributed to Bubb, K. J..

2 recordsLinked to original sources
bioRxiv2026

Eicosapentaenoic Acid Enhances Angiogenesis and Reperfusion After Ischemia: Comparative Effects of Omega-3 Fatty Acids in a Murine Hind Limb Model

BackgroundOmega-3 polyunsaturated fatty acids are known to confer benefits in the prevention of cardiovascular diseases. Among these, eicosapentaenoic acid (EPA) appears to be more effective than docosahexaenoic acid (DHA) in ischemic vascular conditions. However, the specific roles of EPA and DHA in limb angiogenesis and post-ischemic reperfusion remain unclear. Moreover, omega-3 fatty acids remain understudied for peripheral artery disease (PAD) intervention. The aim was to compare the effect of high dose omega-3 fatty acids, EPA and DHA on ischemic tissue reperfusion, angiogenesis and vascular remodelling in mice. MethodsHind limb ischemia (HLI) was performed in mice and reperfusion was measured using laser speckle contrast imaging over two weeks post-HLI. Mice were treated daily with oral high-dose EPA or DHA (600 mg/kg/day) or vehicle (olive oil). Gastrocnemius muscle tissue was collected for analysis of mRNA and protein markers of angiogenesis. ResultsFollowing HLI, blood flow was restored more rapidly in mice treated with EPA compared with vehicle. DHA treatment did not enhance reperfusion. Histological assessment revealed significant muscle fibre regeneration after HLI, which was further improved by EPA. CD31+ neo vessel density was also increased in the EPA group. Collectively, these findings indicate that EPA promotes angiogenesis after peripheral vascular ischemia, whereas DHA does not. The beneficial effects of EPA are associated with upregulation of hypoxia inducible factor . ConclusionsHigh-dose EPA accelerated post-ischemic reperfusion, while DHA was ineffective. These results highlight EPA as a potential therapeutic strategy for improving limb perfusion and vascular repair in patients with PAD. Research PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIOmega-3 fatty acid, eicosapentaenoic acid (EPA) accelerates post-ischaemic reperfusion following hind limb ischemia injury in mice. C_LIO_LIOmega 3 fatty acid, docosahexaenoic acid (DHA), does not show the same improvement in reperfusion after hind limb ischemia C_LIO_LIEPA can promote vasculogenesis and stimulate muscle fibre regeneration. C_LI What question should be addressed next?O_LIHigh dose purified EPA, in the form of icosapent ethyl reduces mortality from coronary artery disease. Peripheral artery disease (PAD) is a common co-morbidity yet high quality interventional trials for icosapent ethyl for PAD are lacking. Therapeutic angiogenesis has the potential to improve PAD symptoms and disease progression but there are no efficacious candidates. Icosapent ethyl should be trialled to determine whether functional outcomes are improved in PAD. C_LI

physiology↗
bioRxiv2025

Perinatal Asphyxia Alters Physiological Responses and Ex Vivo Cardiovascular Function of Preterm Growth-Restricted Lambs

IntroductionFetal growth restriction (FGR) arises from chronic hypoxia and increases the risk of cardiovascular dysfunction following perinatal asphyxia, although the underlying mechanisms are unknown. We investigated whether FGR lambs have altered cardiovascular responses to perinatal asphyxia compared to control lambs, and whether impairments in 1 and {beta}1 adrenergic receptor function underlie these responses. MethodsSingle or twin-bearing ewes underwent sterile fetal surgery at 89 days gestation (dGA; term=148d) to induce FGR (single umbilical artery ligation) or sham surgery (Control). At 126dGA, lambs were delivered via caesarean section, instrumented and randomised to immediate ventilation (ControlVENT n=6; FGRVENT n=6), or asphyxia (ControlASPHYXIA n=12; FGRASPHYXIA n=11) induced by umbilical cord occlusion while withholding resuscitation until diastolic blood pressure (BP) decreased to 10mmHg. Lambs were ventilated for 8 hours before baseline ex vivo cardiac function was assessed via Langendorff perfusion to measure left ventricular developed pressure (LVDP), heart rate (HR) and coronary perfusion pressure (CPP). Ex vivo 1 and {beta}1 adrenergic responses were assessed via phenylephrine (10-5 to 10-2 mmol/L) and dobutamine (10-7 to 10-4) administration, respectively. ResultsFGRASPHYXIA lambs had lower BP during asphyxia (p<0.05 vs ControlASPHYXIA) and took longer to reach a diastolic BP of 10mmHg (14.5 {+/-} 0.8 min vs. 19.2 {+/-} 1.3 min; p=0.005). FGRASPHYXIA lambs had lower BP in the first 5 minutes after return of spontaneous circulation (p<0.05) due to impaired vascular contractility, with reduced Tau, dP/dtmax and dP/dtmin (p<0.03 vs ControlASPHYXIA). Baseline LVDP, HR and CPP were similar between groups, however FGRASPHYXIA lambs had increased LVDP responses to phenylephrine and dobutamine (p<0.05 vs ControlASPHYXIA), without significant changes to HR or CPP. ConclusionFGR lambs have altered physiological responses to perinatal asphyxia due to impaired vascular contractility and dysregulated cardiac 1 and {beta}1 adrenergic receptor function, which may increase susceptibility to cardiovascular dysfunction in the neonatal period.

physiology↗