Acetylation: a "living target" for cardiovascular disease

the world's number one killer, and unfortunately, there is no cure for cardiovascular disease, existing treatments to prevent and improve symptoms.
facing a growing number of patients, the scientific community is eager to hand over the cardiovascular disease "root cure." A growing body of research shows a close relationship between lysine acetylation modification and cardiovascular disease, cancer, and neurological disorders.
Recently, a review published in Nature Review- Cardiology by Professor Ge Dubo, a member of the Chinese Academy of Sciences and dean of Fudan University's Institute of Biomedical Sciences, concluded that lysine acetylation is catalyzed by lysine acetyl transferase (KATs), modified by lysine deacetylase (KDACs), and that KATs and KDACs play a key role in the development of cardiovascular disease.most basic structure and functional unit of the human body is cells, and cells mainly through protein tasks to maintain the balance of the human body. Different tasks require different proteins, some of which are the result of gene-specific expression and are given innate "super-powers";
acetyl-based group is one of the most popular "afterlife" weapons, the application of many scenarios, acetyl-based proteins involved in almost all biological processes of cells, such as transcription, stress response, metabolism and protein synthesis and degradation. Uncovering the mystery of the "modification" of acetylation protein will lay an important foundation for solving the mystery of life of protein modification law.
kats and KDACs regulate gene expression through histamine acetylation. The paper's first author, Dr. Li Peng of Fudan University's Institute of Biomedical Research, said that during the regulatory process, lysine acetylation alters the charge on the lysine residue and changes the protein structure, thus affecting enzyme activity, DNA binding and protein stability. Lysine acetylation at the tail of histogenesis weakens histoprotein-DNA interactions and activates gene transcription. At the same time, acetylation modification also regulates the activity of a large number of non-histoproteins in many important cell processes, which in turn regulate gene transcription, mRNA shearing, signal transducting, metabolism and cell survival of lactating cells.previous studies have found that KATs and KDACs regulate the occurrence and development of cardiovascular disease through lysine acetylation modification. Different types of cardiovascular disease regulation process are different, Ge's team used several common cardiovascular diseases as an example to explain this regulatory process.
high blood pressure is a common cardiovascular disease. Studies of vascular endothyl cells have found that histamine acetylation levels affect the development of hypertension. Deacetylase HDAC3 enhances transcription activity and promotes the development of hypertension by deacetylization. The Sirtuin family's deacetylase SIRT1 regulates the contraction/expansion of blood vessels, and SIRT3 regulates the vitality of mitochondrial proteins, protecting the development of hypertension. It is speculated that deacetylase HDAC3, SIRT1 and SIRT3 may be potential targets for early diagnosis and treatment of hypertension.
In addition, in the heart muscle reconstruction process of heart failure, HDAC4, HDAC5 and HDAC9 inhibit myocardial hypertrophy by inhibiting hypertrophy-related transcription factors, SIRT1, SIRT2, SIRT3 also play a role in inhibiting myocardial hypertrophy, wherein SIRT3 mainly inhibits myocardial fibrosis by regulating mitochondrial function and inhibiting SMAD signal path. At the same time, studies have found that certain types of HDAC can promote pathological heart muscle growth and impair heart function. Accordingly, inhibitors and astenticase inhibitors and agitants may have a protective effect on heart disease reconstruction.
heart attack patients after vascular re-opening treatment, easy to trigger an over-the-cumial myocardial isoemia and perfusion damage, causing additional damage to myocardial cells. The study found that HDAC6 can aggravate isoemia refill damage, while HDAC1 located in myocardial cell mitochondrials also promotes isoemia refill damage. In contrast, SIRT1, SIRT3, and SIR-
T7 mitigate myocardial cell death caused by isoemia and perfusion damage by protecting mitochondrial function or suppressing apoptosis pathps.
refore, inhibitors of HDAC6 and HDAC1 in mitochondrials will be potential drugs to reduce ischemic refill damage in the myocardial muscle after surgery, while the Sirtuin family's aniggerys also contribute to post-infarction recovery.
Li Hua, co-author of the paper and a researcher at Sun Yat-sen Hospital affiliated with Fudan University, said the study suggests that inhibiting the process of promoting disease occurrence and disease recovery can lead to the control of the molecular level of cardiovascular disease.it is not easy to apply the findings to the clinic. Currently, some deacetylase inhibitors have been approved by the U.S. Food and Drug Administration for cancer treatment for their inhibitory effects on vascular regeneration, but some studies have found that they are often associated with the occurrence of roomic arrhyth arrhythmics, resulting in restrictions on the use of these drugs in cardiovascular disease. Therefore, deacetylase-targeted drugs for patients with ishedic heart disease have yet to be further excavated and verified.
addition, some deacetylase inhibitors may be safer and more effective in the treatment of cardiovascular diseases, such as HDAC3 inhibitors for hypertension, HDAC6 inhibitors for the treatment of atrial fibrillation and the mitigation of isoemia refill damage. Unlike other deacetylases, SIRT1, SIRT2, SIRT3, and SIRT5 inhibit the progression of cardiovascular disease. Therefore, Sirtuin astrists such as resveratrol, SRT2104 and niacinamide kerucleose are potential drugs for cardiovascular disease treatment.
researchers say it is worth noting that the current clinical Phase III trial of resveratrol and niacin keruclein for the treatment of external arterial disease, the treatment of resveratrol for dilated cardiomyopathy is under way, and that the clinical IV of water-based bisphenic patients with hypertension The phase trial, completed in 2018, shows that Sirtuin astrists are more convincing in the safety and effectiveness of cardiovascular disease than existing deacetylase inhibitors, and may have clinical value in treating multiple types of cardiovascular disease.
, the focus of future research should be on the design of tissue-specific deacetylase inhibitors or the search for tissue-specific pathological targets. (Source: Bu Ye Huangxin)
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