Alejandro Mata-Daboin's research while affiliated with University of Tennessee and other places

Publications (18)

Article
Endothelial cells (ECs) line the lumen of blood vessels and regulate functions, including contractility. Physiological stimuli, such as acetylcholine (ACh) and intraluminal flow, activate small conductance calcium-activated potassium (SK3) channels in ECs, leading to hyperpolarization and vasodilation. Whether these stimuli modulate SK3 surface abu...
Article
The pathological involvement of anion channels in vascular dysfunction that occurs during type 2 diabetes (T2D) is unclear. Here, we tested the hypothesis that TMEM16A, a calcium (Ca ²⁺ )-activated chloride (Cl ⁻ ) channel, contributes to modifications in arterial contractility during T2D. Our data indicate that T2D increased TMEM16A mRNA in arteri...
Article
Full-text available
PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, produci...
Article
Full-text available
PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, produci...
Article
Full-text available
PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, produci...
Article
Full-text available
PKD2 (polycystin-2, TRPP1) channels are expressed in a wide variety of cell types and can regulate functions, including cell division and contraction. Whether posttranslational modification of PKD2 modifies channel properties is unclear. Similarly uncertain are signaling mechanisms that regulate PKD2 channels in arterial smooth muscle cells (myocyt...
Article
Full-text available
Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture and remodeling, cell migration, and erythrocyte volume. The identity of the membrane components th...
Article
Full-text available
Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth m...
Article
Full-text available
Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth m...
Article
Full-text available
Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth m...
Article
Full-text available
Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth m...

Citations

... Emerging studies have revealed that CaCC, encoded by TMEM16A, is involved in several I/R-induced pathological events, such as myocardial ischemia, arrhythmia, and stroke [12,13,23]. Moreover, its expression has been suggested to be upregulated in many diseases, including hypertension, diabetes, cystic fibrosis, and cancer [8,[24][25][26]. Our previous study demonstrated that TMEM16A was an essential component of CaCC in hepatocytes and increased during nonalcoholic fatty liver disease [9], indicating the involvement of TMEM16A in liver-related disease. ...
... To determine the role of endothelium, neflamapimod-induced vasodilatory responses in endothelium-intact and -denuded mesenteric arteries were compared. To this end, we performed endothelium denudation by slowing passing air bubbles through the vessel lumen and confirming the absence of 1 µM acetylcholine (ACh)-mediated dilation as described previously (Fig. 4a) [25][26][27][28] . Both endothelium-intact and -denuded vessels were preconstricted with 1 µM phenylephrine (PE). ...
... 35,36 Taken together, our results point endothelial dysfunction of resistance arteries specifically due to defective polycystin-1-dependent mechanosensing in EC as a direct and central cause of hypertension in ADPKD. Interestingly, these results extend recent findings from a study using a similar mouse genetic approach, which showed that Pkd2 deficiency in EC also promotes endothelial dysfunction assessed by flow-mediated dilatation and high blood pressure 37 and thus supports the complementary role of polycystin-1 and polycystin-2 in blood flow sensing and mechanotransduction. 6 The functional role of polycystins in arteries is complex and also involves smooth muscle cells. Indeed, as shown by Sharif-Neaini et al, 38 in vascular smooth muscle cells, the polycystin-1/ polycystin-2 ratio controls pressure sensing by regulating the opening of stretch-activated ion channels and deletion of Pkd1 alone reduces arterial myogenic tone. ...
... Mesenteric artery bed was dissected and placed in pre-chilled PSS. Third and fourth order branches of mesenteric arteries (<250 μm) were cleaned of adventitial tissue, cut into 1-2 mm long segments, and cannulated for pressure myography [24,25,26]. ...
... ADPKD is primarily caused by mutations in the PKD-1 and PKD-2 genes that encode the proteins polycystin-1 and polycystin-2, respectively. Polycystin-1 and -2 are expressed on the surface of renal tubular cells, but also in vascular smooth muscle and vascular endothelial cells.[29][30][31] Aside from promoting cyst formation, defects in these proteins are being discussed to be involved in oxidative stress, hypoxia and endothelial dysfunction.5 ...
... Polycystin-1 (PC-1, PKD1) is a receptor-like transmembrane protein encoded by the Pkd1 gene (3). PC-1 is expressed in various cell types, including endothelial cells, and is predicted to form eleven transmembrane helices, an extracellular N-terminus and an intracellular C-terminus (3)(4)(5)(6)(7)(8). The PC-1 N-terminus is large (>3000 amino acid residues) and contains multiple putative adhesion-and ligand-binding sites (3,(7)(8)(9)(10)(11). ...
... Abnormalities of Pkd2 in endothelial cells may contribute to cardiac disease. Pkd2 was knocked out in endothelial cells [30]. Flow-mediated Pkd2 channel activation resulted in calcium influx that activated calcium-activated potassium channels and endothelial nitric oxide synthase (eNOS) in endothelial cells. ...
... Polycystin-2 (PC2) is a transmembrane protein encoded by the PKD2 gene expressed in a variety of cells including ASCs (Hasan et al., 2019). In epithelial cells containing primary cilia, PC2 is colocalized with ciliary polycystin-1 and functions as a component of a mechanosensory complex (Thompson et al., 2021). ...
... The cell membrane is composed of a lipid bilayer; saturated and polyunsaturated fatty acids can, therefore, regulate the activity of the PIEZO1 channel by adjusting membrane stiffness and lipids [32]. Compared with the antagonists of the PIEZO1 channels, Yoda1, the specific agonist of PIEZO1, is highly selective, acting exclusively on the variable binding domain of PIEZO1 [33]. ...
... To determine the role of endothelium, ne amapimod-induced vasodilatory responses in endotheliumintact and -denuded mesenteric arteries were compared. To this end, we performed endothelium denudation by slowing passing air bubbles through the vessel lumen and con rming the absence of 1µM acetylcholine (ACh)-mediated dilation as described previously (Fig 4a) [25][26][27][28] . Both endothelium-intact and -denuded vessels were preconstricted with 1µM phenylephrine (PE). ...