Table 1 Summarized 14 genes that were analyzed in the present study

Solute carrier family 4 member 4 (SLC4A4, also known as NBCe1)

SLC4A4 encodes NBCe1 which is the first eukaryotic Na⁺ − coupled transporter. The transporter is a member of the anion exchange family belonging to the second largest secondary carrier superfamily (APC). A previous GWAS study have revealed that SLC4A4 was hypertension susceptibility gene [12].

NADPH oxidase 3 (Nox3)

Nox3 is a member of the NADPH oxidase (Nox) family of oxidant-generating enzymes. After its original cloning and detection in fetal tissues and inner ear, studies remain limited and its function mostly limited to gravity perception. However, several studies have also reported the physiologic role of Nox3 induction in lungs and lung endothelial cells [7, 13].

Interleukin 6 (IL6)

Interleukin 6 (IL6) is a pleiotropic cytokine with a wide range of biologic function on hematopoiesis, inflammation, immune regulation and oncogenesis. The increasing levels of IL-6 in lung and serum are associated with PH [3].

Transcription factor EC (TFEC)

Transcription factor EC (TFEC) most likely acts as a transcriptional repressor in heterodimers with other microphthalmia-TFE (MiT) family members. The expression of murine TFEC is restricted to macrophages (mTFEC). mTFEC as a macrophage-specific transcription factor plays a critical role in macrophage-specific gene regulation [3]. Considering the activities of macrophages in PH development, TFEC might have potential connection with PH.

Caveolin-1

Caveolin-1, which is a major protein constituent of caveolae, interacts with a variety of signaling molecules implicated in PH. Disruption and progressive loss of endothelial caveolin-1 with reciprocal activation of proliferative pathways occur before the onset of PH, and the rescue of caveolin-1 inhibits proliferative pathways and attenuates PH [4].

NADPH oxidase 4 (Nox4)

NADPH oxidase 4 is the major NADPH oxidase homolog expressed in human PASMCs and its expression both at the mRNA and protein level is significantly increased in lungs from patients with PH, which suggests a correlation between Nox4 and the onset of PH [5, 6]. Additionally, Nox4 acts as a primary source of ROS, contributes to the proliferation and remodeling of PH [7, 8].

Oxidized low density lipoprotein receptor 1 (OLR-1)

Oxidized low density lipoprotein receptor 1 (OLR-1), the receptor for oxidized low-density lipoprotein, is expressed in endothelial cells, macrophages or smooth muscle cells. Recent studies have shown that OLR-1 is involved in the lung inflammation and injury [3].

Thrombospondin 1 (THBS1)

Thrombospondin 1 (THBS1) is a kind of matricellular protein, which is a secreted molecular that has both extracellular matrix and cell surface receptor. In animals, pulmonary THBS1 is upregulated rapidly following hypoxic challenge. Additionally, clinical studies of plasma THBS1 and mutations of THBS1 in PH have been reported [4].

ATPase phospholipid transporting 8B4 (ATP8B4)

ATPase phospholipid transporting 8B4 (ATP8B4) activity is important in ATP biosynthesis and phospholipid transport via a variety of potential mechanisms. A recent whole-exome sequencing research identified that ATP8B4 gene is strongly associated with the risk of development of PH [5].

NADPH oxidase 5 (Nox5)

NADPH oxidase 5 (Nox5) is the last NOX family member to be identified. Caveolin-1 binds directly to Nox5 and suppresses the activity of Nox5. Although the direct connection between Nox5 and PH has not been reported, dysregulation of caveolin-1 has been documented with PH states.

T-box4 (Tbx4)

T-box4 (Tbx4) is a transcription factor in the T-box gene family, which is expressed in variety of organs including mesenchyme of the lung and trachea. Tbx4 has been shown to be involved in lung growth and branching. The function mutations in Tbx4 have been previously reported to be associated with PH [3].

Chromobox 7 (CBX7)

Chromobox 7 (CBX7) is one of the five mammalian orthologues of Drosophila Polycomb. CBX7 was recognized as the main orthologue of Drosophila Polycomb implicated in maintaining the self-renewal of embryonic stem cells. Until now, litter is known about the potential correlation of CBX7 to PH.

Cytochrome b-245 beta chain (CYBB)

The Cytochrome b-245 beta chain (CYBB) gene encodes membrane protein Nox2, which plays a crucial role in stromal interaction molecular 1 (STIM1) activation and in the control of the cytosolic oscillations that drive murine pulmonary microvascular endothelial cells (MPMVECs) activation [4]. Our recent research has also revealed the role of STIM1 during the acute lung intoxication [5].

Galectin-3 (Gal-3)

Galectin-3 (Gal-3) is a β-galactoside binding lectin that regulates multiple pathways. Our recent study has revealed the effectiveness of genetic and pharmacological strategies targeting Gal-3 in halting the progression of PH remodeling and development of experimental PH [1].