Vascular Characteristics and Expression of Hypoxia Genes in Tibetan Pigs' Hearts

Overview

Journal Vet Med Sci

Specialty Veterinary Medicine

Date 2021 Sep 25

PMID 34561963

Citations 9

Authors

Yanan Yang

Caixia Gao

Tianliang Yang

Yuzhu Sha

Yuan Cai

Xinrong Wang

Qiaoli Yang

Chengze Liu

Biao Wang

Shengguo Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Tibetan pigs have exhibited unique characteristics from low-altitudes pigs and adapted well to the Qinghai-Tibet Plateau.

Objectives: The current study was undertaken to investigate the hypoxic adaptation of heart in Tibetan pigs.

Methods: The hearts of Tibetan pigs and Landrace pigs raised at high or low altitudes were compared using 3D casting technology, scanning electron microscopy and real-time quantitative PCR (qRT-PCR).

Results: We found that the ratio of the major axis to the minor axis and the density of the heart were significantly higher in Tibetan pigs than in Landrace pigs (p < 0.05). Tibetan pigs had larger diameters and higher densities of arterioles than Landrace pigs (p < 0.05), and these features have a similar variation with the expression of vascular endothelial growth factor (VEGF). The cardiac expression levels of hypoxia-inducible factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) were significantly higher in pigs reared at high altitudes than in those reared at low altitudes (p < 0.05). In contrast, Egl nine homolog 1 (EGLN1) had the opposite trend with respect to HIF-1α and eNOS and was related to red blood cell (RBC) counts. Notably, the expressions of erythropoietin (EPO) and endothelial PAS domain-containing protein 1 (EPAS1) were significantly higher in Landrace pigs kept at high altitudes than in the others (p < 0.05) and were associated with haemoglobin.

Conclusions: These findings show that the regulation of the heart function of Tibetan pigs in a hypoxic environment is manifested at various levels to ensure the circulation of blood under extreme environmental conditions.

Citing Articles

Enhanced immunity: the gut microbiota changes in high-altitude Tibetan pigs compared to Yorkshire pigs.

Liu C, Dan H, Yang Y, Du Y, Hao Z, Chen L Front Microbiol. 2024; 15:1469253.

PMID: 39624721 PMC: 11609222. DOI: 10.3389/fmicb.2024.1469253.

Genetic characterization of Tibetan pigs adapted to high altitude under natural selection based on a large whole-genome dataset.

Zhang L, Zhu Y, Ren Y, Xu L, Liu X, Qi X Sci Rep. 2024; 14(1):17062.

PMID: 39048584 PMC: 11269713. DOI: 10.1038/s41598-024-65559-3.

Divergence of Liver Lipidomes in Tibetan and Yorkshire Pigs Living at Different Altitudes.

Luo W, Xu Y, Gu X, Zhang J, Wang J, Geng F Molecules. 2023; 28(7).

PMID: 37049754 PMC: 10095695. DOI: 10.3390/molecules28072991.

Characterization of circRNA-miRNA-mRNA networks regulating oxygen utilization in type II alveolar epithelial cells of Tibetan pigs.

Yang Y, Li Y, Yuan H, Liu X, Ren Y, Gao C Front Mol Biosci. 2022; 9:854250.

PMID: 36213124 PMC: 9532862. DOI: 10.3389/fmolb.2022.854250.

Plateau Adaptation Gene Analyses Reveal Transcriptomic, Proteomic, and Dual Omics Expression in the Lung Tissues of Tibetan and Yorkshire Pigs.

Shang P, Zhang B, Li P, Ahmed Z, Hu X, Chamba Y Animals (Basel). 2022; 12(15).

PMID: 35953907 PMC: 9367445. DOI: 10.3390/ani12151919.

References

Avivi A, Shams I, Joel A, Lache O, Levy A, Nevo E . Increased blood vessel density provides the mole rat physiological tolerance to its hypoxic subterranean habitat. FASEB J. 2005; 19(10):1314-6. DOI: 10.1096/fj.04-3414fje. View

Peng Y, Cui C, He Y, Ouzhuluobu , Zhang H, Yang D . Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia. Mol Biol Evol. 2017; 34(4):818-830. PMC: 5400376. DOI: 10.1093/molbev/msw280. View

Xu X, Xu H, Qimuge A, Liu S, Wang H, Hu M . MAPK/AP-1 pathway activation mediates AT1R upregulation and vascular endothelial cells dysfunction under PM2.5 exposure. Ecotoxicol Environ Saf. 2018; 170:188-194. DOI: 10.1016/j.ecoenv.2018.11.124. View

Yu J, Liang F, Huang H, Pirttiniemi P, Yu D . Effects of loading on chondrocyte hypoxia, HIF-1α and VEGF in the mandibular condylar cartilage of young rats. Orthod Craniofac Res. 2017; 21(1):41-47. DOI: 10.1111/ocr.12212. View

Williams A, Ainslie P, Anholm J, Gasho C, Subedi P, Stembridge M . Left Ventricular Twist Is Augmented in Hypoxia by β-Adrenergic-Dependent and β-Adrenergic-Independent Factors, Without Evidence of Endocardial Dysfunction. Circ Cardiovasc Imaging. 2019; 12(5):e008455. DOI: 10.1161/CIRCIMAGING.118.008455. View

Lin C, Lan Y, Ou M, Ji L, Lin S . Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats. J Endocrinol Invest. 2019; 42(11):1307-1317. DOI: 10.1007/s40618-019-01053-2. View

Xu X, Bao Y, Wang X, Yan F, Guo S, Ma Y . Hypoxic-stabilized EPAS1 proteins transactivate DNMT1 and cause promoter hypermethylation and transcription inhibition of EPAS1 in non-small cell lung cancer. FASEB J. 2018; :fj201700715. DOI: 10.1096/fj.201700715. View

Qi X, Zhang Q, He Y, Yang L, Zhang X, Shi P . The Transcriptomic Landscape of Yaks Reveals Molecular Pathways for High Altitude Adaptation. Genome Biol Evol. 2018; 11(1):72-85. PMC: 6320679. DOI: 10.1093/gbe/evy264. View

Zhang B, Chamba Y, Shang P, Wang Z, Ma J, Wang L . Comparative transcriptomic and proteomic analyses provide insights into the key genes involved in high-altitude adaptation in the Tibetan pig. Sci Rep. 2017; 7(1):3654. PMC: 5473931. DOI: 10.1038/s41598-017-03976-3. View

10.

El Hasnaoui-Saadani R, Marchant D, Pichon A, Escoubet B, Pezet M, Hilfiker-Kleiner D . Epo deficiency alters cardiac adaptation to chronic hypoxia. Respir Physiol Neurobiol. 2013; 186(2):146-54. DOI: 10.1016/j.resp.2013.01.003. View

11.

Beall C, Cavalleri G, Deng L, Elston R, Gao Y, Knight J . Natural selection on EPAS1 (HIF2alpha) associated with low hemoglobin concentration in Tibetan highlanders. Proc Natl Acad Sci U S A. 2010; 107(25):11459-64. PMC: 2895075. DOI: 10.1073/pnas.1002443107. View

12.

Depoix C, de Selliers I, Hubinont C, Debieve F . HIF1A and EPAS1 potentiate hypoxia-induced upregulation of inhibin alpha chain expression in human term cytotrophoblasts in vitro. Mol Hum Reprod. 2017; 23(3):199-209. DOI: 10.1093/molehr/gax002. View

13.

Kim H, Yoo H, Lin H, Oh G, Zhang Y, Kim S . Role of muscular eNOS in skeletal arteries: Endothelium-independent hypoxic vasoconstriction of the femoral artery is impaired in eNOS-deficient mice. Am J Physiol Cell Physiol. 2016; 311(3):C508-17. DOI: 10.1152/ajpcell.00061.2016. View

14.

Srinivasan S, Chitalia V, Meyer R, Hartsough E, Mehta M, Harrold I . Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis. Angiogenesis. 2015; 18(4):449-62. PMC: 4600037. DOI: 10.1007/s10456-015-9468-3. View

15.

Xu Z, Rothstein S . ROS-Induced anthocyanin production provides feedback protection by scavenging ROS and maintaining photosynthetic capacity in Arabidopsis. Plant Signal Behav. 2018; 13(3):e1451708. PMC: 5927679. DOI: 10.1080/15592324.2018.1451708. View

16.

Yang Y, Gao C, Yang T, Sha Y, Cai Y, Wang X . Characteristics of Tibetan pig lung tissue in response to a hypoxic environment on the Qinghai-Tibet Plateau. Arch Anim Breed. 2021; 64(1):283-292. PMC: 8253108. DOI: 10.5194/aab-64-283-2021. View

17.

Shoda T, Futamura K, Orihara K, Emi-Sugie M, Saito H, Matsumoto K . Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation. Allergol Int. 2015; 65(1):21-9. DOI: 10.1016/j.alit.2015.08.001. View

18.

Vozdek R, Long Y, Ma D . The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury. Sci Signal. 2018; 11(550). DOI: 10.1126/scisignal.aat0138. View

19.

Yang Y, Gao C, Yang T, Sha Y, Cai Y, Wang X . Vascular characteristics and expression of hypoxia genes in Tibetan pigs' hearts. Vet Med Sci. 2021; 8(1):177-186. PMC: 8788992. DOI: 10.1002/vms3.639. View

20.

Shakhsheer B, Lec B, Zaborin A, Guyton K, Defnet A, Bagrodia N . Lack of evidence for tissue hypoxia as a contributing factor in anastomotic leak following colon anastomosis and segmental devascularization in rats. Int J Colorectal Dis. 2016; 32(4):539-547. DOI: 10.1007/s00384-016-2737-9. View