Microvascular research · 2025
Vascular diameter and responsiveness to soluble guanylate cyclase modulators: A systematic review of preclinical and clinical evidence.
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Josef M S
Аннотация
BACKGROUND: Vessel diameter has been proposed as a determinant of responsiveness to soluble guanylate cyclase (sGC) modulators, but available evidence remains heterogeneous across species and experimental settings. Understanding these relationships is important for improving translational interpretation and therapeutic use of sGC stimulators and activators.
METHODS: A systematic review was performed according to PRISMA principles, identifying in vitro, in vivo, and clinical studies that examined vascular or signaling responses to sGC stimulators or activators in vessels of defined diameter. Data were extracted on vessel type, size, species, disease model, compound class, and measured outcomes such as vasorelaxation or cyclic guanosine monophosphate (cGMP) production. Methodological quality and risk of bias were assessed using SYRCLE, Cochrane RoB 2.0, and ROBINS-I tools. Additional relevant studies identified after the main search were summarized as supporting evidence.
RESULTS: Fifty-three studies met inclusion criteria (thirty-eight preclinical, fifteen clinical). In general, smaller vessels showed stronger relaxation and higher cGMP responses to sGC activators, while the evidence for sGC stimulators was more heterogeneous and less consistently diameter-dependent. The magnitude of this relationship varied with species, vascular bed, and oxidative or pathological conditions. Human tissue studies often lacked information on pre-analytical factors such as ischemia time or donor characteristics. Across study designs, risk-of-bias assessment indicated predominantly moderate or high risk, largely due to incomplete methodological reporting and limited control for confounding.
CONCLUSIONS: Current evidence supports a size-dependent pattern of vascular responsiveness to sGC modulators, but inference strength is constrained by heterogeneous methodologies and inconsistent reporting. Future work should implement standardized vessel classification, rigorous biospecimen handling, and transparent methodological documentation to clarify the clinical significance of vessel diameter in sGC-based therapy.
METHODS: A systematic review was performed according to PRISMA principles, identifying in vitro, in vivo, and clinical studies that examined vascular or signaling responses to sGC stimulators or activators in vessels of defined diameter. Data were extracted on vessel type, size, species, disease model, compound class, and measured outcomes such as vasorelaxation or cyclic guanosine monophosphate (cGMP) production. Methodological quality and risk of bias were assessed using SYRCLE, Cochrane RoB 2.0, and ROBINS-I tools. Additional relevant studies identified after the main search were summarized as supporting evidence.
RESULTS: Fifty-three studies met inclusion criteria (thirty-eight preclinical, fifteen clinical). In general, smaller vessels showed stronger relaxation and higher cGMP responses to sGC activators, while the evidence for sGC stimulators was more heterogeneous and less consistently diameter-dependent. The magnitude of this relationship varied with species, vascular bed, and oxidative or pathological conditions. Human tissue studies often lacked information on pre-analytical factors such as ischemia time or donor characteristics. Across study designs, risk-of-bias assessment indicated predominantly moderate or high risk, largely due to incomplete methodological reporting and limited control for confounding.
CONCLUSIONS: Current evidence supports a size-dependent pattern of vascular responsiveness to sGC modulators, but inference strength is constrained by heterogeneous methodologies and inconsistent reporting. Future work should implement standardized vessel classification, rigorous biospecimen handling, and transparent methodological documentation to clarify the clinical significance of vessel diameter in sGC-based therapy.