Malignant Cardiovascular Disease Research Articles

Upregulation of eIF2α by m6A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.

Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m6A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m6A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.

ATF3 in atherosclerosis: a controversial transcription factor.

Atherosclerosis, the pathophysiological basis of most malignant cardiovascular diseases, remains a global concern. Transcription factors play a key role in regulating cell function and disease progression in developmental signaling pathways involved in atherosclerosis. Activated transcription factor (ATF) 3 is an adaptive response gene in the ATF/cAMP response element binding (CREB) protein family that acts as a transcription suppressor or activator by forming homodimers or heterodimers with other ATF/CREB members. Appropriate ATF3 expression is vital for normal physiological cell function. Notably, ATF3 exhibits distinct roles in vascular endothelial cells, macrophages, and the liver, which will also be described in detail. This review provides a new perspective for atherosclerosis therapy by summarizing the mechanism of ATF3 in atherosclerosis, as well as the structure and pathophysiological properties of ATF3. KEY MESSAGES: • In endothelial cells, ATF3 overexpression aggravates oxidative stress and inflammation. • In macrophages and liver cells, ATF3 can act as a negative regulator of inflammation and promote cholesterol metabolism. • ATF3 can be used as a potential therapeutic factor in the treatment of atherosclerosis.

Multiscale Encoding of Electrocardiogram Signals with a Residual Network for the Detection of Atrial Fibrillation.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, and it is an indication of high-risk factors for stroke, myocardial ischemia, and other malignant cardiovascular diseases. Most of the existing AF detection methods typically convert one-dimensional time-series electrocardiogram (ECG) signals into two-dimensional representations to train a deep and complex AF detection system, which results in heavy training computation and high implementation costs. In this paper, a multiscale signal encoding scheme is proposed to improve feature representation and detection performance without the need for using any transformation or handcrafted feature engineering techniques. The proposed scheme uses different kernel sizes to produce the encoded signal by using multiple streams that are passed into a one-dimensional sequence of blocks of a residual convolutional neural network (ResNet) to extract representative features from the input ECG signal. This also allows networks to grow in breadth rather than in depth, thus reducing the computing time by using the parallel processing capability of deep learning networks. We investigated the effects of the use of a different number of streams with different kernel sizes on the performance. Experiments were carried out for a performance evaluation using the publicly available PhysioNet CinC Challenge 2017 dataset. The proposed multiscale encoding scheme outperformed existing deep learning-based methods with an average F1 score of 98.54%, but with a lower network complexity.

Deciphering the Molecular Role of Non-coding RNA in Malignant Cardiac Disease

Non-coding RNA (NcRNA) is a functional RNA which contributes to the gene regulation at both transcriptional and post-transcriptional level. NcRNA lack in the encoding of proteins, but this does not counteract the generic functioning of the cells. It is a group of RNA with versatile functioning. They are classified into small nuclear RNA, tRNA, rRNA, and microRNA. The cumulative functioning of ncRNA includes slicing as well as the management of chromosomes. The long ncRNA plays a vital role in malignant cardiovascular disease such as atherosclerosis, myocardial infarction, and injury. They act by different pathways and undergo different mechanisms that include binding to CBX, activating mesoderm posterior-1, modulating MKX25, and targeting bone morphogenetic proteins. They have an intricate role in cardiovascular disorders as some of the long ncRNAs contribute to the inhibition of plague formation in the heart, thus reducing the risk for atherosclerosis and thus retarding the development of heart failure. Whereby microRNA acts as a prognostic biomarker in the early detection of heart injury. MicroRNA has even been identified for the inhibition of angiogenesis, and Piwi-interacting RNA is important in genetic diversity. Thus, ncRNA is one of the factors in the leading cause of malignant cardiac disorder and is responsible for cardiac remodelling andheart failure.