An inducible model for medial calcification based on matrix Gla protein deficiency.

Calcific deposits in the arterial media have been associated with a number of metabolic and genetic disorders including diabetes, chronic kidney disease and generalized arterial calcification of infancy. The loss of matrix Gla protein (MGP) leads to medial elastic lamina calcification (elastocalcinosis) in both humans and animal models. While MGP-deficient (Mgp) mice have been used as a reliable model to study medial elastocalcinosis, these mice are difficult to maintain because of their fragility.

Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia.

Matrix Gla protein (MGP) is a vitamin K-dependent post-translationally modified protein, highly expressed in vascular and cartilaginous tissues. It is a potent inhibitor of extracellular matrix mineralization. Biallelic loss-of-function variants in the MGP gene cause Keutel syndrome, an autosomal recessive disorder characterized by widespread calcification of various cartilaginous tissues and skeletal and vascular anomalies.

Elastin calcification in in vitro models and its prevention by MGP's N-terminal peptide.

Medial calcification has been associated with diabetes, chronic kidney disease, and genetic disorders like pseudoxanthoma elasticum. Recently, we showed that genetic reduction of arterial elastin content reduces the severity of medial calcification in matrix Gla protein (MGP)-deficient and Eln haploinsufficient Mgp-/-;Eln+/- mice. This study suggests that there might be a direct effect of elastin amount on medial calcification.

Differences in mineral composition and morphology between men and women in aortic valve calcification.

Aortic valve calcification leads to the deposition of calcium phosphate minerals in the extracellular matrix of the aortic valve leaflets. The mineral deposits can severely narrow the opening of the aortic valve, leading to aortic stenosis. There are no therapies to halt or slow down disease progression and the mechanisms governing aortic valve calcification are still poorly understood.

Effect of the Ionic Concentration of Simulated Body Fluid on the Minerals Formed on Cross-Linked Elastin-Like Polypeptide Membranes.

Deposition of calcium phosphate minerals on the elastin-rich medial layers of arteries can cause severe cardiovascular complications. There are no available treatments for medial calcification, and the mechanism of mineral formation on elastin layers is still unknown. We recently developed an in vitro model of medial calcification using cross-linked elastin-like polypeptide (ELP) membranes immersed in simulated body fluid (SBF).

Urotensin II, urotensin-related peptide, and their receptor in aortic valve stenosis.

Objectives: Aortic valve stenosis (AVS) is the most common cause of surgical valve replacement worldwide. The vasoactive peptide urotensin II (UII) is upregulated in atherosclerosis and several other cardiovascular diseases; however, its role in the pathogenesis of AVS remains to be determined. Here, we investigated the expression of UII, urotensin-related peptide (URP), and the urotensin receptor (UT) and the role this system plays in AVS.

Inorganic ions on hemozoin surface provide a glimpse into Plasmodium biology.

In malaria, Plasmodium parasites produce hemozoin (Hz) as a route to detoxify free heme released from the catabolism of hemoglobin. Hz isolated from the parasites is encapsulated in an organic layer constituted by parasite and host components. This organic coating may play a role in Hz formation and in the immunomodulatory properties attributed to Hz, and they may influence the mode of action of antimalarials that block Hz formation.

Cross-Linked Elastin-like Polypeptide Membranes as a Model for Medial Arterial Calcification.

Calcium phosphate minerals deposit on the elastin-rich medial layers of arteries in the majority of seniors, diabetic, and chronic kidney disease patients, causing severe cardiovascular complications. There is no cure for medial calcification, and the mechanism of mineral formation on elastin layers is unknown. Here we propose cross-linked elastin-like polypeptide membranes as models to study medial calcification.

Lipoprotein(a) Induces Human Aortic Valve Interstitial Cell Calcification.

Lipoprotein(a), or Lp(a), significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001). Inhibition of MAPK38 and GSK3β significantly reduced Lp(a)-induced calcification of human aortic valve interstitial cells (p < 0.

Raman Spectroscopy for Inverted Papilloma: A Proof-of-Concept Study.

Inverted papillomas are tumors of the sinonasal tract with a propensity to recur. Raman spectroscopy can potentially identify inverted papillomas from other tissue based on biochemical signatures. A pilot study comparing Raman spectroscopy to histopathology for 3 types of sinonasal tissue was performed.

Multidisciplinary Approach to Understand Medial Arterial Calcification.

Objective: Vascular calcification significantly increases morbidity in life-threatening diseases, and no treatments are available because of lack of understanding of the underlying molecular mechanism. Here, we study the physicochemical details of mineral nucleation and growth in an animal model that faithfully recapitulates medial arterial calcification in humans, to understand how pathological calcification is initiated on the vascular extracellular matrix.

Approach And Results: MGP (matrix Gla protein) is a potent mineralization inhibitor.

Role of Noncanonical Wnt Signaling Pathway in Human Aortic Valve Calcification.

Objective: The mechanisms underlying the pathogenesis of aortic valve calcification remain unclear. With accumulating evidence demonstrating that valve calcification recapitulates bone development, the crucial roles of noncanonical Wnt ligands WNT5a, WNT5b, and WNT11 in osteogenesis make them critical targets in the study of aortic valve calcification.

Approach And Results: Using immunohistochemistry, real-time qPCR, Western blotting, and tissue culture, we examined the tissue distribution of WNT5a, WNT5b, and WNT11 in noncalcified and calcified aortic valves and their effects on human aortic valve interstitial cells (HAVICs).