Ribosome and Atherosclerosis

Atherosclerosis is a health condition that manifests through the stiffening and narrowing of arteries due to the layers of plaque buildup. This plaque consists of excess fat, cholesterol, and other substances, which impedes blood flow, leading to severe health repercussions like heart attacks or strokes. This condition is propelled by the unusual multiplication of vascular smooth muscle cells (VSMCs) and persistent inflammation. Ribosome biogenesis, which is crucial for the creation of ribosomes, has been associated with this abnormal VSMC multiplication and the onset of atherosclerosis. The unanticipated link between ribosomes and atherosclerosis reveals new pathways for understanding and treating this disease.

The Role of Ribosomes in Atherosclerosis

Decoding the Role of Ribosomes in Atherosclerosis Ribosome biogenesis features essential processes such as the synthesis of ribosomal RNA (rRNA) and ribosomal proteins, and the assembly to form mature ribosomes—all of these are closely connected with the emergence of atherosclerosis. The PeBoW complex—comprising of PES-BOP1-WDR12—is instrumental in the maturation of rRNA during ribosome assembly. Enhanced expression of BOP1 and PES1, both constituents of the PeBoW complex, stimulate ribosome biogenesis, subsequently leading to abnormal VSMC multiplication and atherosclerosis. Moreover, regulators of ribosome biogenesis like nucleolin (Ncl) have links to atherosclerosis. Ncl reinforces the stability of ABCA1, which facilitates cholesterol efflux and prevents the buildup of lipid and foam cell formation. Oxidized low-density lipoprotein (oxLDL), a known instigator of atherosclerosis, can increase Ncl expression in VSMCs, which in turn propels VSMC multiplication and alterations in the cell cycle.

Fig. 1 Ribosomes and atherosclerosis.¹

Potential Therapies for Atherosclerosis Targeting Ribosomes

Inhibiting ribosome biogenesis has emerged as a potential therapeutic approach for inhibiting the abnormal proliferation of VSMCs and slowing down the progression of atherosclerosis. Several studies have identified key components of the ribosome biogenesis pathway that could be targeted for therapeutic intervention.

• One such target is the PES-BOP1-WDR12 (PeBoW) complex, which is involved in the maturation of rRNA. Inhibiting the activity of the PeBoW complex could potentially inhibit neointimal hyperplasia and slow down the development of atherosclerosis.
• Another potential target is circARNL, which inhibits ribosome biogenesis by occupying the pre-rRNA site of the PeBoW complex member PES1 and inhibiting the cleavage of pre-rRNA. Inhibiting circARNL could potentially inhibit VSMC proliferation and delay the progression of atherosclerosis.
• Curcumin, a natural compound with anti-inflammatory properties, has been shown to effectively inhibit VSMC proliferation and slow down the development of atherosclerosis. The mechanism of action involves the promotion of DNMN2 expression, which in turn elevates the levels of 18S rRNA methylation. This suggests that targeting the methylation of rRNA could be a potential therapeutic strategy for atherosclerosis.

In sum, developing treatments to target both ribosomal biogenesis and inflammation show great promise for atherosclerosis therapy. The next stage consists of further investigating the effectiveness and safety of these potential treatments in both preclinical and clinical environments.

Here at Creative Biolabs, our skilled and knowledgeable team specializes in ribosomal research and are always ready to provide a wide range of services. This includes the customization of Ribosome Separation and Extraction Services and Ribosome Analysis Services for our global customer base. If there are specific requests or if additional details are needed regarding these services, don't hesitate to contact us. We are always delighted to provide detailed information and a price quotation for you.

Reference

1. Jiao, Lijuan, et al. "Ribosome biogenesis in disease: new players and therapeutic targets." Signal Transduction and Targeted Therapy 8.1 (2023): 15.