Medial vascular smooth muscle cells (VSMCs) in normal adults are lowly proliferative, synthetic, and secretory but rich in contractile proteins. Upon stimulation, they transdifferentiate into synthetic phenotype and lively divide, migrate, and secrete extracellular matrix (ECM) proteins and active protein factors Muto et al., 2007), excessively expanding in the media and intima as seen in pulmonary hypertension (PAH) and atherosclerosis (AS). They also attenuate proliferation along with their aging and damage from oxidative stress or organ failure (McCrann et al., 2008) and conduct the irregular apoptosis as shown in aneurysms (Lu et al., 2021). As one major pathological change in cardiovascular diseases (CVDs), the abnormal VSMC populating persisting due to chronic and repetitive injury and stimulation, will remodel vascular structure and function and promote CVDs finally.

Long non-coding RNAs (lncRNAs) are the non-coding RNAs that are longer than 200 nucleotides and carry a ploy A-tail and cap structure (Kopp and Mendell, 2018, Zhang et al., 2019a). They can directly bind to DNA, RNA, or proteins and act as signals, decoys, guides, and scaffolds, broadly affecting cell epigenetics, gene transcription and post-transcription, and post-translational modification (Wang and Chang, 2011). Among these regulatory activities, their role in post-transcriptional regulation is particularly appreciated notably. So far, most lncRNAs have been revealed to act as competing endogenous RNAs (ceRNAs) and compete with the other transcripts including mRNAs through their corresponding miRNA response elements (MREs) for shared microRNAs (miRNAs), thereby modulating the mRNA stability and translation of multiple signaling molecules and transcription factors (Qi et al., 2015). Besides, lncRNAs are shown to alter the expression level of miRNAs, negatively in most cases, which further intensifies their modulation of target mRNAs at the post-transcriptional level. Interestingly, certain lncRNAs even directly interact with protein targets and affect their stability, as exampled by the lncRNA ZNF800/PTEN axis (Lu et al., 2020).

In recent time, mounting lncRNAs have been revealed to be closely related to and modulate CVD development, especially contributing to irregular VSMC growth (Simion et al., 2019). They alter their own expression in VSMCs in response to various pathological conditionsand work through multiple action axes to regulate VSMC proliferation, migration, and survival.

Here we discuss the lately uncovered lncRNAs that control the VSMC growth in three major harmful CVDs: atherosclerosis, pulmonary hypertension, and aneurysms (Table 1). The emphasis is put on the clearly characterized axes of lncRNA/direct target/final protein targets and their effects on the signaling pathways, transcription, and epigenetic behaviors of VSMCs.