# Evaluation of myocardial microcirculation changes in rats from different altitudes based on CT myocardial perfusion imaging

**Authors:** Chunlong Yan, Jinfeng Ma, Tingjun Yan, Yanqiu Sun

PMC · DOI: 10.1016/j.bbrep.2025.102417 · Biochemistry and Biophysics Reports · 2026-01-06

## TL;DR

This study shows that high-altitude exposure in rats leads to reduced heart blood flow and structural changes, possibly linked to a protein called HIF-2α.

## Contribution

The study identifies HIF-2α as a key mediator of altitude-induced myocardial microcirculation changes in rats.

## Key findings

- Myocardial perfusion parameters like TTP and MTT increased with higher altitude.
- HIF-2α showed greater sensitivity to altitude changes compared to other hypoxia markers.
- High-altitude exposure caused structural heart remodeling and altered blood parameters.

## Abstract

This study employed computed tomography myocardial perfusion imaging (CT-MPI) to investigate myocardial microcirculation changes in rats across different altitudes. Four-week-old male Sprague-Dawley rats were allocated into plain (450 m), moderate-altitude (MA, 2200 m), and high-altitude (HA-A, 3800 m; HA-B, 4200 m) groups. After 28 weeks, CT-MPI revealed significant altitude-dependent alterations in myocardial perfusion parameters: TTP and MTT increased while BF and BV decreased (P < 0.05). Accompanying these changes were modifications in blood parameters—including red blood cell indices, white blood cell counts, and biochemical markers—along with myocardial structural remodeling characterized by disordered cell arrangement, widened intercellular gaps, and increased collagen deposition. Molecular analyses demonstrated variations in mRNA and protein expression of hypoxia-related markers (CD34, EPO, VEGF, HIF-1α, HIF-2α) and collagen types I/III, with HIF-2α exhibiting particular sensitivity to altitude variation. These findings indicate that high-altitude exposure induces progressive myocardial microcirculation impairment coupled with hematological adaptations and tissue remodeling, potentially mediated through HIF-2α-regulated hypoxia response pathways.

•Alterations in myocardial microcirculation in rats from different altitude regions.•With increasing altitude, rat hearts exhibit a hypoperfusion state.•We hypothesize that HIF-2α exhibits greater sensitivity to changes in altitude.

Alterations in myocardial microcirculation in rats from different altitude regions.

With increasing altitude, rat hearts exhibit a hypoperfusion state.

We hypothesize that HIF-2α exhibits greater sensitivity to changes in altitude.

## Linked entities

- **Genes:** CD34 (CD34 molecule) [NCBI Gene 947], EPO (erythropoietin) [NCBI Gene 2056], VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091], EPAS1 (endothelial PAS domain protein 1) [NCBI Gene 2034]

## Full-text entities

- **Genes:** Epas1 (endothelial PAS domain protein 1) [NCBI Gene 29452] {aka HIF-2 alpha, HIF2 alpha, HLF, Hif2a}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Epo (erythropoietin) [NCBI Gene 24335], Cd34 (CD34 molecule) [NCBI Gene 305081]
- **Diseases:** myocardial (MESH:D009202), hypoxia (MESH:D000860)
- **Chemicals:** MTT (MESH:C070243)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12808609/full.md

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12808609/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12808609/full.md

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Source: https://tomesphere.com/paper/PMC12808609