Emodin alleviates aortic valvular calcification by inhibiting the AKT/FOXO1 pathway

Man Luo1, Wei Sun1, Bin Zhou1

  • 1Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Insights

Emodin effectively alleviates high-calcium-induced valvular calcification by suppressing AKT/FOXO1 signaling. This natural compound shows promise as a therapeutic strategy for treating valvular calcification in patients.

Area of Science:

  • Biomedical research
  • Pharmacology
  • Cardiovascular disease

Background:

  • Valvular calcification is a growing health concern, particularly in the elderly.
  • Current treatments for valvular calcification are limited, highlighting the need for new therapeutic agents.

Purpose of the Study:

  • To investigate the suppressive effects of emodin on high-calcium-induced valvular calcification.
  • To elucidate the underlying molecular mechanisms of emodin's action.

Main Methods:

  • Valvular calcification was induced in mice using vitamin D.
  • Porcine aortic valve interstitial cells (PAVICs) were used to assess emodin's effects on cell viability, apoptosis, and osteogenic gene expression.
  • The role of AKT/FOXO1 signaling was examined using specific activators and inhibitors.

Main Results:

  • Emodin (5 μM) reduced calcium accumulation and osteogenic gene upregulation in PAVICs under high-calcium conditions.
  • In vivo, emodin treatment decreased calcium content in serum, valves, and arteries of mice with induced valvular calcification.
  • Emodin reversed the upregulation of p-AKT and p-FOXO1, key components of the AKT/FOXO1 signaling pathway.

Conclusions:

  • Emodin demonstrates a significant therapeutic potential in alleviating valvular calcification.
  • The mechanism involves the suppression of the AKT/FOXO1 signaling pathway.
  • These findings offer novel insights for developing emodin-based treatments for clinical valvular calcification.
Abstract

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.4K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.0K
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
553
Antihypertensive Drugs: Action of Calcium Channel Blockers01:18

Antihypertensive Drugs: Action of Calcium Channel Blockers

Calcium ions are essential to contract smooth muscle cells in blood vessels. They enter these cells through voltage-dependent calcium channels, specifically L-type calcium channels in the cell membrane. These L-type calcium channels are integral to the excitation-contraction coupling process in smooth muscle. When a stimulus is received by smooth muscle cells, their membrane depolarizes. This alteration in membrane potential instigates the opening of L-type calcium channels. As a result,...
913
Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.3K
Aortic Regurgitation III: Medical Management01:25

Aortic Regurgitation III: Medical Management

Aortic regurgitation (AR) is when the aortic valve does not close or seal properly, leading to backward blood circulation from the aorta into the left ventricle during diastole. Common causes of AR include rheumatic heart disease, congenital valve defects, and aortic root dilation. Managing AR requires a multifaceted approach to alleviate symptoms, preserve left ventricular function, and address the underlying cause of the regurgitation. Patients with symptomatic AR or significant left...
65