PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating

Feng Liu1,2, Jinyong Chen1,2, Wangxing Hu1,2

  • 1Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Insights

Protein tyrosine phosphatase 1B (PTP1B) inhibition shows promise for treating calcific aortic valve disease (CAVD). Targeting PTP1B may prevent aortic valve calcification by preserving mitochondrial function.

Area of Science:

  • Biochemistry
  • Cardiovascular Biology
  • Pharmacology

Background:

  • Calcific aortic valve disease (CAVD) lacks effective pharmacological treatments.
  • Protein tyrosine phosphatase 1B (PTP1B) is implicated in disease pathogenesis.

Purpose of the Study:

  • To investigate the role of PTP1B in CAVD.
  • To evaluate the therapeutic potential of PTP1B inhibition in CAVD.

Main Methods:

  • Assessed PTP1B expression in human calcified aortic valves.
  • Examined the effects of PTP1B inhibition on valvular interstitial cells and LDLR-/- mice.
  • Investigated PTP1B's interaction with OPA1 in mitochondrial homeostasis and osteogenesis.

Main Results:

  • PTP1B was upregulated in calcified human aortic valves.
  • PTP1B inhibition reduced the fibrocalcific response in vitro and in vivo.
  • PTP1B regulates mitochondrial homeostasis via OPA1 isoform transition, impacting valvular interstitial cell osteogenesis.

Conclusions:

  • PTP1B plays a critical role in CAVD pathogenesis.
  • PTP1B inhibition demonstrates therapeutic potential for CAVD.
  • Targeting PTP1B may offer a novel strategy for preventing aortic valve calcification.

Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
15.1K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
12.0K
Hormones and Bone Tissue01:17

Hormones and Bone Tissue

The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
2.9K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.8K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
245
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K