Key result
Preeclampsia is linked to reduced microvascular calcium spark and transient outward current frequencies.
Why the study?
The mechanisms underlying maternal microvascular dysfunction in preeclampsia had not been fully defined, and the Ca 2+ sparks-BK Ca vasodilatory axis had not previously been assessed in this disorder.
Case-Control
Microvascular arteries in preeclampsia exhibit reduced Ca2+ spark frequency and spontaneous transient outward currents due to increased SERCA2 inhibition by unphosphorylated PLN, identifying potential therapeutic targets for restoring vascular function.
Hypothesis-generating for microvascular dysfunction in preeclampsia; requires validation before any clinical translation.
BACKGROUND: Maternal microvascular dysfunction is a hallmark of the hypertensive pregnancy disorder preeclampsia, but the mechanism(s) have not been fully defined. Within vascular smooth muscle cells, the principal pressure-induced vasodilatory pathway depends on localized Ca 2+ -release events from the sarcoplasmic reticulum ryanodine receptors (Ca 2+ sparks), which stimulate BK Ca (large-conductance Ca 2+ -activated potassium channels) to cause spontaneous transient outward currents and vasorelaxation. Here, the Ca 2+ sparks–BK Ca axis is assessed in preeclampsia for the first time. METHODS: Pressurized omental resistance arteries from normotensive pregnant women and women with preeclampsia were imaged by high-speed spinning-disk laser confocal microscopy to assess Ca 2+ sparks (20–110 mm Hg) and caffeine-evoked Ca 2+ release (10 mmol/L; 80 mm Hg). Electrophysiology was used to assess spontaneous transient outward currents (−60 to 0 mV) and BK Ca currents (−100 to +100 mV) in isolated vascular smooth muscle cells. A liquid chromatography–selected reaction monitoring–tandem mass spectrometry assay measured SERCA2 (sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase-2) and unphosphorylated/phosphorylated proteoforms of regulatory PLN (phospholamban). Vasoactive effects of the BK Ca -dependent vasorelaxant HBD2 (human β-defensin-2; 0.01–10 nmol/L) were assessed by wire myography. RESULTS: In microvascular arteries from women with preeclampsia, there was reduced Ca 2+ spark frequency ( P =1.1×10 − 10 ) and spontaneous transient outward current frequency ( P =0.023). There was also reduced sarcoplasmic reticulum Ca 2+ release in response to caffeine ( P =0.0013), reduced sarcoplasmic reticulum refilling ( P =2.0×10 − 4 ), and decreased ratio of SERCA2 to inhibitory unphosphorylated PLN ( P =0.030), implicating increased SERCA2 inhibition. HBD2 (0.01–10 nmol/L) caused BK Ca -dependent relaxation ( P =4.6×10 − 10 ) of omental arteries without affecting Ca 2+ spark frequency. CONCLUSIONS: In microvascular arteries from women with preeclampsia, there is a striking reduction in Ca 2+ spark frequency and spontaneous transient outward currents, likely secondary to increased inhibition of SERCA2 by unphosphorylated PLN and reduced sarcoplasmic reticulum Ca 2+ load. These defects may provide novel therapeutic targets to restore physiological control of the vasculature. BK Ca -mediated relaxation by HBD2 was independent of Ca 2+ sparks, supporting vasodilatory strategies bypassing disrupted microvascular mechanisms in preeclampsia.
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Parnell et al. (2026) conducted a case-control in Preeclampsia. Preeclampsia vs. Normotensive pregnancy was evaluated on Ca2+ spark frequency and spontaneous transient outward current frequency in microvascular arteries (p=1.1×10−10). Preeclampsia was associated with reduced microvascular Ca2+ spark frequency (P=1.1×10−10) and spontaneous transient outward current frequency (P=0.023) compared with normotensive pregnancy.
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