In a multicenter international study, OSA was shown to independently predict adverse cardiovascular events. Therefore, a new potential treatment method for preventing the progression of ACS has emerged, that is, active treatment OSA. However, at present, the pathogenesis and effective treatment of OSA for ACS remain unclear. Hence, it is imperative to explore the molecular mechanism of the ACS after OCS to determine efficient biomarkers and effective approaches for the diagnosis, monitoring, as well as treatment of patients.
Herein, 17 genes in the UA and 43 genes in MI linked to OSA were uncovered for functional analysis using the GO, as well as the KEGG enrichment assessments. Additionally, the PPARG gene comprised one of the hub genes uncovered by the PPI network. PPARG can adjust the balance between glucose and fatty acid oxidation, which plays an important role in the reconstruction of human myocardial infarction after ischemia28–30. Moreover, previous evidence has suggested that PPARG may be a risk factor for cardiovascular diseases such as metabolic syndrome, obesity, diabetes and hypertension31–33. PPARG is a member of the nuclear hormone receptor superfamily, which can recruit transcriptional coactivators necessary to initiate the transcription of target genes and may also play a protective role in the development of MI34,35. At the same time, Cao et al. also confirmed that THERE was a significant correlation between PPARG and protection of MI36.
The cleaved product of the glycoprotein amyloid precursor protein is AB, which aggregates into AB plaques. According to the amyloid cascade hypothesis, it is these plaques that are responsible for AD pathology37. Soluble Ab species can bind to and produce toxicity to various neuronal receptors, leading to cellular oxidative stress and epigenetic-mediated transcription disorders38. However, recent studies have shown that soluble Ab has beneficial physiological effects on certain functions, such as regulating cellular signaling pathways and synaptic function39. The main driving force of the pathological progression of AD is the accumulation of A in the brain, which leads to synaptic loss and neuronal cell death40–42. In addition, some evidence has found that the continuous accumulation of cerebrovascular A plays A role in cerebral microhemorrhage 43,44 and vascular cognitive impairment45.
CD40 is a costimulatory molecule in the constitutive expression of B lymphocytes and is expressed in a variety of cells, such as endothelial cells (ECs), monocytes, macrophages and smooth muscle cells (SMCs)46. In Antoniades et al. 's study, CD40 was found to be involved in the immune pathogenesis of ACS 47 due to its bi-cellular activation through the signaling pathways C-Jun, NF-κB and ERK 1/2, resulting in the secretion of inflammatory cytokines, adhesion molecules, and platelet activation46. However, soluble forms of CD40 and CD40L were significantly associated with adverse cardiovascular events in patients with ACS48,49, suggesting that they are potential targets for potential therapeutic agents 47.
MMP9 has been shown in many studies to be significantly associated with cardiovascular disease. Moreover, it was also confirmed in our results that MMP9 was highly expressed in both datasets. MMP9 is a protease of the MMP family that is capable of degrading a broad spectrum of extracellular matrix components and is held responsible for vascular remodeling and breakdown of the fibrous cap of atherosclerotic lesions leading to plaque vulnerability50. MMPs are a family of zinc-dependent proteinases capable of degrading various structural components of ECM, thus leading to ECM destruction and plaque rupture51.
MAPK1 is mostly concentrated in the cytoplasm, and activated MAPK1 translocates to the nucleus and activates the expression of target genes in tumor tissues52. Many previous studies have demonstrated that MAPK1 plays an important role in atherosclerotic lesions or processes53–55. Furthermore, MAPK1 were both up-regulated in Coronary heart disease (CAD)56. At the same time, MAPK pathway also plays a role in stroke progression57,58.
In addition to the genes described above that are known to be associated with coronary heart disease, we also found four potential targeted genes that have not been clearly reported in the literature.
MAPK3 referred to as the mitogen-activated protein kinase 3, is a MAP kinase family member and participates in an extensive array of biological processes, including cell proliferation, as well as angiogenesis. MAPK3 may serve as the intrafollicular mediators that trigger the expansion of the cumulus cell-oocyte complex (COC), as well as the maturation of the oocytes59–61. The extracellular, as well as intracellular mitogenic stimuli activate the MAPK3 cascade, which has pivotal functions in cellular differentiation, proliferation and survival62. The study of colorectal cancer by Schmitz et al. showed that the expression of MAPK3 is related to poor prognosis63.
Angiotensin (AGT) is a plasma globulin of the silk fibroin family, is converted to angiotensin I by renin. Angiotensin converting enzyme (ACE) cleaves angiotensin I and converts to angiotensin II. Angiotensin II then causes increased arterial pressure by participating in intravascular fluid volume elevation and vasoconstriction. Finally, angiotensin II functions through angiotensin receptor type 1 (AGTR1) and angiotensin receptor type 2 (AGTR2)64–67.
According to previous reports68–73, TGFβ1 is secreted by a variety of cells, such as peripheral blood monocytes, macrophages, platelets, vascular smooth muscle cells (VSMCs), and renal cells. Its regulatory function on the vessel wall is directed at VSMC, endothelial cells and extracellular matrix. Although there is a significant correlation between TGFβ1 and the pathogenesis of atherosclerosis, the relationship between plasma TGFβ1 levels and the risk of ACS remains unclear69,74−76. This is because the exact mechanism of TGFβ1 signaling in the vascular system is still not fully understood70,71,73,77.
The CD40L gene consists of five exons and four introns. Studies have shown that if CD40L expression is low or not expressed, impaired immunoglobulin class-switching while mice overexpressing CD40L have chronic inflammation78. Notably, a dinucleotide microsatellite with cytosine-adenine (CA) repeats in the CD40LG 3-untranslated region (3-UTR) described as highly polymorphisms have been found to be associated with multiple diseases, such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA).79–81.