CVDs are caused by a reduced flow of oxygenated blood in the human body. CVDs are a group of diseases, including ACS, MI, AS, CH, RHD, MF, PAH, and ARR [1,2]. CVDs are the major cause of death worldwide, according to the World Health Organisation; 17.9 million deaths were reported in 2019, accounting for 32% of all deaths at the global level. Early diagnosis and targeted treatment of CVDs remain challenges [3,4]. Current treatment options are available, with their limitations, and can reduce disease development. Novel treatment options are required to target cellular events during disease progression to facilitate the timely management of the patient’s clinical conditions [5]. Multiple coding genes are involved in the development of CVDs. In recent years, it has been discovered that non-coding RNA (ncRNA) regulates disease development [6]. The ncRNAs are 200-nt base sequences that regulate the genetic, epigenetic, and cell signalling mechanisms, as well as gene expression [7]. ncRNAs are used as biomarkers for diagnosis and treatment due to their involvement in disease severity. In recent years, ncRNA has been investigated in CVDs [8]. ncRNAs have great importance in clinical applications and are classified into various categories, including miRNAs, lncRNAs, and circRNAs [9]. SiRNAs can be used to target ncRNAs. RNAi-mediated siRNAs are highly adaptable and are used to silence their mRNA’s protein-encoding gene. MiRNAs are 22-nucleotide RNA molecules that regulate cell signalling and downregulate the expression of specific genes by modifying the translation process [10].

The miRNA lin-4 was identified in 1993 in Caenorhabditis [71]. The synthesis of miRNA occurs in the nucleus and is transcribed by RNA polymerase II into coding and noncoding, capping polyadenylated pri-miRNAs. The pre-miRNA produces a hairpin-like structure and is timed by the Drosha nuclear enzyme, then transported to the cytoplasm [12]. The DICER removes the terminal loop of the pri-miRNAs, resulting in a 20-25 nucleotide base pair dsRNA complex. The dsRNA, as attached to the miRNA-linked RISC (RNA-induced silencing complex), targets mRNAs and results in mRNA de-adenylation and translational repression (Figure 1) [13]. In vivo and in vitro studies have shown that miRNA plays a critical role in the regulation of CVDs such as CH, HF, ARR, ACS, MI, AS, RHD, and PAH (Table 2) [14].

Myocardial hypertrophy (MH) is caused by the development of CVDs, including stenosis of the heart valve and hypertension, and causes HF and death [75]. Several miRNAs, including miR-208a, miR-19a/b, miR-34a, miR-145, miR-150, miR-378, and others, are involved in the development of MH [76]. MiR-378 is an anti-MH miRNA and regulates the Igf1r (insulin-like growth factor receptor), Grb2 (growth factor receptor binding protein 2), and Ksr1 (Ras kinase inhibitor 1) [77]. MiR-185 regulates cardiac cell proliferation and is related to the signal transduction mechanism. MiR-34a regulates the Agt9a gene, which is involved in autophagy. The transcription activator p300 is regulated by miR-150 [78]. MiR-1 is involved in the growth and development of cardiomyocytes by reducing the expression of GATA-binding protein 4 (GATA4) and calmodulin Mef2a, which regulate the calcium signal pathway and protein expression and could be targeted for diagnosis and therapy [79].

HF is caused by a failure of the regulatory mechanism in the heart [80]. Many different forms of miRNA, such as miR-320a, miR-423-5p, miR-200b, miR-622, miR-1228, miR-208b, miR-499, miR-223, miR-1254, miR-1306, miR-18a, miR-26b, miR-27a, miR-30e, miR-106a, miR-199a, are crucial in the development of HF conditions [81]. Early hypertrophic growth in the left ventricle may be caused by miR-125b and lead to HF. The expression of brain natriuretic peptide (BNP) is regulated by miR-200b, miR-622, and miR-1228. HF may also be caused by increased expression of miR-208b and miR-499. These miRNA regulations in HF could be targeted for diagnosis and therapeutic approaches [82].

Arrhythmias (AR) are mainly caused by imbalances of the ion channel and dysregulations of conduction in cardiac muscles. Atrial fibrillation (AF) is a severe AR observed in CVDs that can lead to HF, stroke, and death [83]. There are various types of miRNA involved in the development of AR in CVD patients, including miR-664, miR-133, miR-590, miR-130a, miR-21, miR-208b, miR-483, miR-1, and miR-150. In addition, the AF is controlled by the miRNAs miR-328, miR-2, miR-664, miR-483, miR-133, miR-1, miR-208b, miR-590, miR-328, and miR-223 [84]. The overexpression of miR-130a is linked with cx43 (protein connexin 43). MiR-150 regulates the platelet count in patients with AF, which plays a major role in fibrosis and inflammation and is involved in the development of AF [85].

ACS (acute coronary syndrome) is developed by reduced blood flow in the heart, an immediate blockage of the coronary arteries, and localized heart necrosis, all contribute to the development of AMI (acute myocardial infractions) [86]. AMI patients have a high level of miR-1 expression. MiR-1, miR-133a, and miR-208a levels have been found to be higher in AMI patients. Cardiac arrest is regulated by miR-208b and miR-499-5p in patients with coronary artery bypass grafting [87]. These two miRNAs are expressed by dysregulated cardiac muscles. A reduced level of expression has been shown in AMI patients. The expression profile of all these miRNA regulations can be used for early diagnosis and treatment [88]. High miR-208 expression levels have been observed in a mouse model with AMI. High-throughput analysis of miRNA expression in patients with AMI can be explored further for sensitive and specific early diagnosis and treatment [89].

The miRNA plays an important role in the generation of atherosclerosis by vascular angiogenesis, endothelial dysfunction, lipid accumulation, local inflammation, calcification, thrombosis, and endothelial dysfunction [90]. Play important in the development of CAD (coronary artery disease), causes significant death at global level. Expression profile of miRNA has been investigated in patients with AS. MiR-33 regulates the AS disease progression by involving the inflammatory response, cell cycle progression, lipid metabolism, and proliferation [91]. In patients with AS, miR-122 is substantially expressed. MiR-122 controls the levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL).Leukocyte aggregation on endothelial cells is triggered by miR-126-mediated upregulation of VCAM-1 (vascular cell adhesion molecule-1) [92]. Mi-R1 regulates the signalling pathways for MLCK (Myosin Light Chain Kinase) and ERK (Extracellular Signal-Regulated Kinase). MiR-221 and miR-222 control the growth and development of vascular smooth muscle cells (VSMCs). In patients with AS, there is generally less miR-126, miR-1, and miR-221/222 expression [93].

RHD lesions have primarily been found in the mitral valve. RHD tissue and plasma samples have significant levels of miRNA-1299 and miRNA-1183 expression. MiR-328-3p is found in RHD and AF (atrial fibrillation) patients [94]. MiRNA-432 expression levels have been found to be lower in RHD patients. All these microRNAs could be used for early diagnosis. Further investigations are needed to find out more about miRNA regulations in RHD [95].

LncRNAs are more complex and heterogeneous in nature in comparison to miRNAs, which regulate gene expression. LncRNAs are involved in CVDs and categorized into various classes based on their structure and functions, including bidirectional lncRNAs, enhancer lncRNAs, sense lncRNAs, antisense lncRNAs, intergenic lncRNAs, and intron lncRNAs [96]. The gene expression level is changed by the interactions of lncRNA with DNA, RNA, proteins, elements of the chromatin modification complex, and transcription factors. Guided lncRNAs can either activate lncRNA processes or suppress gene expression by delocalizing regulatory elements [97,98,99]. Ribonucleoprotein (RNP) complex formation involves the scaffold lncRNAs (Figure 2). The lncRNAs serve as primary miRNA precursors that are converted into mature miRNAs while the miRNA precursor is suppressed. Long-range gene regulation begins when the lncRNA activates transcription from regulatory areas of the genome. LncRNAs interact with miRNAs and disrupt the RNA molecules’ regulatory system (Figure 3) [97]. lncRNAs also act as a maternal or paternal genomic imprinting expression and help in the development of organisms [100,101]. Regulations and clinical importance of lncRNA in cardiovascular are shown in Table 3.

The integration of various types of cells, the vascular system, and blood vessels are all involved in the generation of the heart [98]. lncRNAs, also known as super-enhancer lncRNAs (SE-lncRNAs), control transcription at the tissue and cell levels. MyoD is an important transcription factor that involves muscle cell differentiation along with other core transcription factors [99]. The CE (core enhancer element) is produced by CERNA, which acts as a positive feedback regulator. It has been recently observed that various types of lncRNA are involved in the development of CVDs, including CHRF, Myh7, LIPCAR, MIAT, Carl, LIPCAR, ASB9P1, RP11-218 M11.6, G078882, G064270, G000678, G030563, H19, TUG1, PFL, MIAT, AK081284, HOXA11-ASz, NRON, and GAS5 [96]. H19 is expressed during embryogenesis and CVD but is repressed after birth. miRNA-675 acts as a negative regulator in cardiac hypertrophy. miR-675-3p and miR-675-5p are upregulated in cardiac hypertrophy [100]. Some pro-hypertrophic factors are also involved in CH and are mediated by Ca/calmodulin-dependent protein kinase IIδ (CaMKIIδ). The lncRNA–miRNA–mRNA axis can be a potential target for therapeutic approaches [101]. All these investigations have confirmed that lncRNAs play major roles in cardiovascular biology and diseases (Table 3) [102].