In response to stressful environments such as oxidative stress, heat shock, UV radiation and viral infection, one of the major defense mechanisms of eukaryotic cells is the formation of stress granules (SGs), dynamic membrane-free organelles composed of mRNA, RNA-binding proteins and translation factors.SGs represent more than just the dynamic sorting of mRNA between translation and decay, but also perform other cellular functions.SGs have been shown to be central to the pathogenesis of a group of closely related degenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myopathy (IBM). However, their role in cardiovascular disease (CVD) is unclear. Scientists have found that the accumulation of SGs can be observed in vascular smooth muscle cells and macrophages and affect the process of atherosclerosis.

Fig. 1. Stress granules are dynamic and have multiple fates. (Protter DSW, et al., 2016)

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SGs are involved in the regulation of CVD, but their role in atrial fibrillation and their relationship to CVD such as atherosclerosis are not known. Our technical team used an unbiased Mass-SPEC-based proteomics approach to identify proteins involved in RNA processing in vascular smooth muscle cells to identify candidate proteins as SG fractions. In addition, we built well-established in vitro and animal models to characterize the proteins that comprise SGs in CVD, including oxidized low-density lipoprotein (oxLDL), PABP, the RBPs HuR, FXR11, CALR3, NEXN, and TPM1, etc.

CD BioSciences offers specialized services to analyze the role of LLPS-mediated SGs in cardiovascular disease, with a special focus on myocardial infarction, coronary artery disease, atherosclerosis, and dilated cardiomyopathy. We aim to help our clients analyze SGs' kinetics, their composition and their function in the context of CVD.

What attracts our clients is that our experts are also committed to developing SGs-based therapeutic strategies for CVD, including:

• Protein Level Control SGs
  We regulate SG kinetics and selective protein recruitment through post-translational modifications (PTM) that allow easy control of SG protein phase separation. We can achieve different types of PTM, including phosphorylation, acetylation, glycosylation, arginine methylation, ubiquitination, SUMOylation, eIF5A, etc.
• Regulation of SGs at the RNA level
  We provide methods to disrupt RNA availability, such as enzymatic degradation (e.g., RNaseA, RNaseL) or inhibition of polyribosome catabolism (e.g., actinomycin, emetine) to rapidly solubilize SGs.

Based on our advanced cell biology methods, mass spectrometry-based proteomics, real-time single-molecule imaging techniques, machine learning and other computational methods, we provide you with more information about the kinetics and function of SGs. In addition, we are developing simple artificial SGs systems constructed in vitro or from cell lysates as well as characterizing CVD-related states that contribute to the modification and mutation of SGs-resident proteins.

CD BioSciences aims to provide you with a comprehensive analysis of the role of SGs mediated by LLPS in the cardiovascular system and to develop new targets for the prevention and treatment of cardiovascular diseases. Our services are widely used in preclinical research in cardiovascular diseases biology, diagnosis and treatment. If you are interested in our services, please feel free to contact us.