RESUMO
Atherosclerosis is a chronic immuno-inflammatory disease, however, the immune landscape and regulatory mechanisms have not been clear. We detected seven principal immune cell clusters with distinct phenotypic and spatial characteristics using single-cell RNA-sequencing of aortic immune cells from patients with acute coronary syndrome and stable angina pectoris. Then we acquired 265 differentially expressed immune-related genes and the high scores were mainly found in T cells and monocytes, which were differentially regulated in atherosclerotic coronary plaques. The CCL signaling pathway was the most relevant pattern in the T cells and CCL5-CCR1 and CCL5-CCR5 ligand-receptor pairs played a vital role in the CCL signaling pathway. Further comparative analysis indicated MCH-I signaling was the most relevant pattern in the T cells and HLA ligand-related ligand-receptor pairs played a vital role. Functional analysis of the single-cell and bulk transcriptomics pointed to multiple pathways, such as antigen presentation and immune response. Nineteen common differentially expressed immune-related genes were found in both immune cells and the human peripheral blood mononuclear cells. Nine common differentially expressed transcription factors were differentially expressed in both T cell and monocyte clusters from the coronary plaques and human peripheral blood mononuclear cells and the network demonstrated that CEBPB might play an essential role in the transcriptional regulation of atherosclerosis as a hub transcription factor. The definition of immune cell diversity and heterogeneity by single-cell level analysis of aortic immune cell subsets not only unveils cell-type-specific pathways and new immune mechanisms but also discovers the functional correlation of immune cells in human atherosclerosis. Our findings provide great promise for the discovery of novel molecular mechanisms and precise therapeutic targets for atherosclerosis.
RESUMO
PURPOSE OF REVIEW: This review sought to summarize the current emerging soluble guanylate cyclase activators and stimulators in patients with heart failure, both heart failure with reduced and preserved ejection fraction, to provide a reference for soluble guanylate cyclase activators and stimulators discovery. RECENT FINDINGS: Heart failure is a common disease with considerable morbidity, hospitalization, and mortality Soluble guanylate cyclase is a key enzyme in the nitric oxide signaling pathway and has attracted rapidly growing interest as a therapeutic target in heart failure. Currently, several soluble guanylate cyclase agonists are in clinical development. Cinaciguat and praliciguat have shown no clear clinical benefit in patients with heart failure in clinical trials. Riociguat increased the 6-min walk distance, cardiac index, and stroke volume index as well as decreased N-terminal pro-B-type natriuretic peptide. Although these populations cover nearly every range of ejection fractions, these were not clinical trials directly in patients with heart failure but were designed in patients with pulmonary hypertension. Vericiguat is recommended in the latest American guideline for patients with heart failure with reduced ejection fraction; however, it gets mixed results in patients with heart failure with preserved ejection fraction. To date, only vericiguat reduces the composite of death from cardiovascular causes or first hospitalization for heart failure in patients with heart failure with reduced ejection fraction and riociguat might improve clinical symptoms and quality of life in patients with heart failure, both heart failure with reduced and preserved ejection fraction. We need more exploration about soluble guanylate cyclase activators and stimulators in patients with heart failure.