Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

Leonetti, Simone; Tricò, Domenico; Nesti, Lorenzo; Baldi, Simona; Kozàkovà, M.; Gonçalves, Isabel; Nilsson, Jan; Shore, Angela C.; Khan, Faisel; Natali, Andrea

doi:10.1016/j.atherosclerosis.2022.01.003

Cited by 9 publications

(7 citation statements)

References 59 publications

(65 reference statements)

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“…HBEGF is a heparin‐binding EGF‐like growth factor and associated with smooth muscle cell migration. It could serve as a biomarker of atherosclerosis extension in patients with evidence of carotid artery atherosclerosis 47 . Vascular endothelial cells could release soluble HBEGF to activate the epidermal growth factor receptor and propel the phosphorylation of JNK2, mediating sorafenib‐induced hand–foot skin reaction 48 .…”

Section: Discussionmentioning

confidence: 99%

“…To evidence of carotid artery atherosclerosis. 47 Vascular endothelial cells could release soluble HBEGF to activate the epidermal growth factor receptor and propel the phosphorylation of JNK2, mediating sorafenib-induced hand-foot skin reaction. 48 More importantly, it played a role in HBEGF-EGF receptor axis, in which oxidated phospholipids induced IL-8 in human aortic endothelial cells during the process of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

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Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction

et al. 2023

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Background Erectile dysfunction and atherosclerosis are common cardiovascular complications in diseases. Clinical associations between erectile dysfunction and atherosclerosis have been noticed, but the specific mechanisms are not illustrated adequately. Objectives The aim of the study was to further mine associated pathological mechanisms and genetic alterations of atherosclerosis in diabetes mellitus‐related erectile dysfunction. Materials and methods Significant atherosclerosis‐related genes were identified from transcriptome data of diabetes mellitus‐related erectile dysfunction and atherosclerosis‐related gene sets from DisGeNET and GeneCard databases. Functional enrichment and immune infiltration analyses were performed to clarify the biological roles and pathways as well as immune responses of significant atherosclerosis‐related gene sets. A protein–protein interaction network was constructed, and gene clusters were performed. Then, data of diabetic plaques and high‐glucose cavernosum endothelial cells were analyzed for validation. And hub atherosclerosis‐related gene sets were identified. Finally, expressed pattern of hub atherosclerosis‐related gene sets were explored by single‐cell profiling and immune analysis. Results In total, 202 significant atherosclerosis‐related gene sets including 100 upregulated and 102 downregulated genes were identified. These genes were related to endothelial cell migration, inflammatory response, regulation of oxidative stress, and immune response. In immune infiltration, immature dendritic cells and monocytes showed differential expression between the diabetes mellitus‐related erectile dysfunction and control groups, A protein–protein interaction network containing 135 nodes was constructed. A hub atherosclerosis‐related gene set signature consisting of HBEGF, LOX, NQO1, and VLDLR was obtained by multi‐omics validation. In addition, Functional enrichment analysis revealed that hub atherosclerosis‐related gene sets were involved in oxidoreductase activity and extracellular matrix organization. Discussion and conclusion We explored atherosclerosis‐related genetic changes and signaling pathways in diabetes mellitus‐related erectile dysfunction. HBEGF, LOX, NQO1, and VLDLR were identified as hub atherosclerosis‐related gene sets. These may serve as potential biomarkers for the clinical management of atherosclerosis and preventing further cardiovascular risks in diabetes mellitus‐related erectile dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction

et al. 2023

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“…This leads to the oxidation of LDL, absorption by platelets, and accumulation of oxidized LDL in them [12], because platelets are the main place of their presence in the blood [5]. It should be noted that CD40L is considered a significant prognostic biomarker of the instability of the course and progression of CVD [16].…”

Section: Discussionmentioning

confidence: 99%

“…Öå ïðèçâîäèòü äî îêñèäàö³¿ ËÏÍÙ, ïîãëèíàííÿ òðîìáîöèòàìè òà íàãðîìàäaeåííÿ â íèõ îêèñëåíèõ ËÏÍÙ [12], áî òðîìáîöèòè º îñíîâíèì ì³ñöåì ¿õ çíàõîäaeåííÿ â êðîâ³ [5]. Ñë³ä çàóâàaeèòè, ùî CD40L ââàaeàºòüñÿ çíà-÷óùèì ïðîãíîñòè÷íèì á³îìàðêåðîì íåñòà-á³ëüíîñò³ ïåðåá³ãó òà ïðîãðåñóâàííÿ ÑÑÕ [16] Âèâ³ëüíåííÿ ïðîçàïàëüíîãî é ³ìóíîðåãóëÿòîðíîãî ö³òîê³íó IL-1 àêòèâîâàíèìè òðîìáîöèòàìè íå ëèøå ³í³ö³þº àäãåç³þ ëåé-êîöèò³â äî åíäîòåë³þ òà ¿õ òðàíñì³ãðàö³þ, àëå é ³íäóêóº ñèíòåç öèòîê³í³â ð³çíèìè êë³òèíàìè, ùî â ê³íöåâîìó ðåçóëüòàò³ ìîaeå âèçíà÷àòè ñêåðîâàí³ñòü ðîçâèòêó ðåàêö³é â àâòî³ìóííî- ìó ÷è àâòîçàïàëüíîìó íàïðÿìêó [17,23,27]. Àêòèâîâàí³ òðîìáîöèòè ³íäóêóþòü IL-1β-çàëåaeíó ñåêðåö³þ åíäîòåë³îöèòàìè IL-6 ³ IL-8, õåìîê³íó CCL2, çá³ëüøóþòü íà åíäîòåë³àëüíèõ êë³òèíàõ åêñïðåñ³þ ìîëåêóë àäãåç³¿ ICAM-1, αvβ3 òà ñåêðåö³þ íèìè õåìîàòðàêòàíòíîãî ïðîòå¿íó-1 (MCP-1), ÷èì ñïðèÿþòü çàëó÷åííþ â ïðîöåñ ìîíîöèò³â [13].…”

Section: îáãîâîðåííÿunclassified

Relationships Between Lipid Profile and Complete Blood Cell Count Parameters

Dzis

Tomashevska

Petrukh³

2022

AML

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Aim. Given that blood cells play an important role in both atherogenesis and lipid metabolism, the research aimed to assess the specifics of the relationship between the parameters of the blood lipid spectrum and the complete blood count (CBC). Materials and Methods. A total of 475 individuals (245 female and 230 male) were included in the study, who simultaneously underwent CBC and determination of lipid profile, namely: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Statistical processing of the obtained data was carried out using the "Statistica for Windows 6.0" software package (Statsoft, USA). Results. An increase in levels of TC and LDL-C was associated with an increase in the count of lymphocytes and erythrocytes. A rise in VLDL-C and, accordingly, TG levels, as well as a decrease in the level of HDL-C, were associated with an increase in the total leukocyte count in the blood without a significant change in the ratio of their different types, and an increase in erythrocyte sedimentation rate. The count of platelets was directly related to the level of LDL-C and increased in the case of a combination of elevated levels of LDL-C and TG. Discussion. The obtained results indicate that the disposal of excess lipoproteins is based on various types of immune reactions. An increase in the levels of VLDL-C and TG is associated with the development of a nonspecific leukocyte reaction, and an increase in LDL-C levels is associated with a more specific platelet-lymphocytic response. A simultaneous increase in LDL-C and TG levels can be associated with the development of both specific and non-specific immune reactions. An increase in the level of HDL-C leads to a decrease in the intensity of innate and adaptive immune responses. Therefore, the lipid profile of patients should be evaluated by taking into account the blood cell counts, especially in the process of hypolipidemic treatment. Conclusions. An atherogenic lipid profile is associated with increased counts of all blood cells, reflecting specific and nonspecific immune reactions in response to elevated levels of various lipid groups. Platelets play an important role in lipid metabolism. Connection of the research with scientific programs, plans, and topics. The study is a fragment of the planned scientific research of the Department of Internal Medicine No. 2 of the Danylo Halytsky Lviv National Medical University: "Peculiarities and markers of the course of internal diseases under conditions of combination with metabolic syndrome and metabolically associated fatty liver disease", state registration number: 0122U000165.

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“…Current proteomic technologies can be broadly characterised as mass spectrometry-based, antibody-based, or aptamer-based, but the broad dynamic range of proteins is often a hurdle for comprehensive and scalable characterisation of the proteome that is under active development [46]. Still, proteins have the advantage of being functionally closer to phenotypes and reflecting some environmental factors, such as smoking [47] or diet [48,49], making them well-suited for predicting disease risk [50][51][52], and yielding insights into mechanistic pathways [53,54]. In addition, proteins are translatable to a broad range of therapeutic modalities for drug discovery but such applications require the additional burden of establishing a causal role in disease.…”

Section: Proteomementioning

confidence: 99%

From ‘Omics to Multi-omics Technologies: the Discovery of Novel Causal Mediators

Mohammadi-Shemirani

Sood

Paré

2023

Curr Atheroscler Rep

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Purpose of Review ‘Omics studies provide a comprehensive characterisation of a biological entity, such as the genome, epigenome, transcriptome, proteome, metabolome, or microbiome. This review covers the unique properties of these types of ‘omics and their roles as causal mediators in cardiovascular disease. Moreover, applications and challenges of integrating multiple types of ‘omics data to increase predictive power, improve causal inference, and elucidate biological mechanisms are discussed. Recent Findings Multi-omics approaches are growing in adoption as they provide orthogonal evidence and overcome the limitations of individual types of ‘omics data. Studies with multiple types of ‘omics data have improved the diagnosis and prediction of disease states and afforded a deeper understanding of underlying pathophysiological mechanisms, beyond any single type of ‘omics data. For instance, disease-associated loci in the genome can be supplemented with other ‘omics to prioritise causal genes and understand the function of non-coding variants. Alternatively, techniques, such as Mendelian randomisation, can leverage genetics to provide evidence supporting a causal role for disease-associated molecules, and elucidate their role in disease pathogenesis. Summary As technologies improve, costs for ‘omics studies will continue to fall and datasets will become increasingly accessible to researchers. The intrinsically unbiased nature of ‘omics data is well-suited to exploratory analyses that discover causal mediators of disease, and multi-omics is an emerging discipline that leverages the strengths of each type of ‘omics data to provide insights greater than the sum of its parts.

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Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

Cited by 9 publications

References 59 publications

Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction

Identifying potential cross‐talk signatures for the occurrence of atherosclerosis in diabetic erectile dysfunction

Relationships Between Lipid Profile and Complete Blood Cell Count Parameters

From ‘Omics to Multi-omics Technologies: the Discovery of Novel Causal Mediators

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