Regulation of Blood Pressure by Targeting Ca
            <sub>V</sub>
            1.2-Galectin-1 Protein Interaction

Hu, Zhenyu; Li, Guang; Wang, Jiong‐Wei; Chong, Suet Yen; Yu, Dejie; Wang, Xiaoyuan; Soon, Jia-Lin; Liang, Mui Cheng; Wong, Yuk Peng; Huang, Na; Colecraft, Henry M.; Liao, Ping; Soong, Tuck Wah

doi:10.1161/circulationaha.117.031231

Cited by 28 publications

(30 citation statements)

References 37 publications

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“…Data were analyzed using FlowJo (BD) software (v10.1). Osmotic minipump (Alzet 2004 - Rate: 0.25 μl/hr; Durect, Cupertino, CA) was implanted subcutaneously immediately before MI surgery as previously described 25 to infuse continuously the peptides (a PAR1 agonist peptide TFLLR-NH2, a PAR2 antagonist peptide FSLLRY-NH2, or a control peptide RLLFT-NH2) at 3 mg·kg -1 ·day -1 for 28 days in TF∆CT mice. Cardiac function was assessed with a high frequency ultrasound system Vevo® 2100 22 .…”

Section: Methodsmentioning

confidence: 99%

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

et al. 2021

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The coagulation protein tissue factor (TF) regulates inflammation and angiogenesis via its cytoplasmic domain in infection, cancer and diabetes. While TF is highly abundant in the heart and is implicated in cardiac pathology, the contribution of its cytoplasmic domain to post-infarct myocardial injury and adverse left ventricular (LV) remodeling remains unknown. Methods: Myocardial infarction was induced in wild-type mice or mice lacking the TF cytoplasmic domain (TF∆CT) by occlusion of the left anterior descending coronary artery. Heart function was monitored with echocardiography. Heart tissue was collected at different time-points for histological, molecular and flow cytometry analysis. Results: Compared with wild-type mice, TF∆CT had a higher survival rate during a 28-day follow-up after myocardial infarction. Among surviving mice, TF∆CT mice had better cardiac function and less LV remodeling than wild-type mice. The overall improvement of post-infarct cardiac performance in TF∆CT mice, as revealed by speckle-tracking strain analysis, was attributed to reduced myocardial deformation in the peri-infarct region. Histological analysis demonstrated that TF∆CT hearts had in the infarct area greater proliferation of myofibroblasts and better scar formation. Compared with wild-type hearts, infarcted TF∆CT hearts showed less infiltration of proinflammatory cells with concomitant lower expression of protease-activated receptor-1 (PAR1) - Rac1 axis. In particular, infarcted TF∆CT hearts displayed markedly lower ratios of inflammatory M1 macrophages and reparative M2 macrophages (M1/M2). In vitro experiment with primary macrophages demonstrated that deletion of the TF cytoplasmic domain inhibited macrophage polarization toward the M1 phenotype. Furthermore, infarcted TF∆CT hearts presented markedly higher peri-infarct vessel density associated with enhanced endothelial cell proliferation and higher expression of PAR2 and PAR2-associated pro-angiogenic pathway factors. Finally, the overall cardioprotective effects observed in TF∆CT mice could be abolished by subcutaneously infusing a cocktail of PAR1-activating peptide and PAR2-inhibiting peptide via osmotic minipumps. Conclusions: Our findings demonstrate that the TF cytoplasmic domain exacerbates post-infarct cardiac injury and adverse LV remodeling via differential regulation of inflammation and angiogenesis. Targeted inhibition of the TF cytoplasmic domain-mediated intracellular signaling may ameliorate post-infarct LV remodeling without perturbing coagulation.

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Section: Methodsmentioning

confidence: 99%

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

et al. 2021

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“…In smooth muscle, CaV1.2 is the main regulator of calcium entry responsible for myocyte contraction and its overexpression is usually associated with hypertension [33,34]. It was shown recently that Galectin-1 (Gal-1) interacts with the intracellular I-II loop of CaV1.2 channels and competes for this site with β2 subunits [35]. The disruption of CaV1.2-β2 interaction by Gal-1 leads to CaV1.2 degradation by the proteasome.…”

Section: Targeting Voltage-dependent Calcium Channel Interactionsmentioning

confidence: 99%

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Noyer

Lemonnier

Mariot

et al. 2019

IJMS

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The characterization of calcium channel interactome in the last decades opened a new way of perceiving ion channel function and regulation. Partner proteins of ion channels can now be considered as major components of the calcium homeostatic mechanisms, while the reinforcement or disruption of their interaction with the channel units now represents an attractive target in research and therapeutics. In this review we will focus on the targeting of calcium channel partner proteins in order to act on the channel activity, and on its consequences for cell and organism physiology. Given the recent advances in the partner proteins’ identification, characterization, as well as in the resolution of their interaction domain structures, we will develop the latest findings on the interacting proteins of the following channels: voltage-dependent calcium channels, transient receptor potential and ORAI channels, and inositol 1,4,5-trisphosphate receptor.

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“…Interestingly, effects on vascular reactivity could be associated to calcium influx in VSMCs, since intracellular Gal-1 has been shown to inhibit ICa ,L modifying the Ca v 1.2 calcium channel in a splice variant-dependent manner [ 66 ]. In this regard, Gal-1 promotes Ca v 1.2 degradation in smooth muscle cells controlling vascular reactivity and blood pressure [ 67 ]. Moreover, Gal-1 has also been implicated in the pathogenesis of preeclampsia, which is characterized by hypertension and proteinuria during pregnancy [ 68 ], suggesting new roles for this lectin in pulmonary, systemic, and pregnancy-induced arterial hypertension.…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities

Seropián

Gónzalez

Maller

et al. 2018

Mediators of Inflammation

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Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, controls immune cell homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-cell apoptotic programs, promoting expansion of T regulatory (Treg) cells, and deactivating antigen-presenting cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses. Here, we discuss the emerging roles of Gal-1 in cardiovascular diseases including acute myocardial infarction, heart failure, Chagas cardiomyopathy, pulmonary hypertension, and ischemic stroke, highlighting underlying anti-inflammatory mechanisms and therapeutic opportunities. Whereas Gal-1 administration emerges as a potential novel treatment option in acute myocardial infarction and ischemic stroke, Gal-1 blockade may contribute to attenuate pulmonary arterial hypertension.

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Regulation of Blood Pressure by Targeting Ca _V 1.2-Galectin-1 Protein Interaction

Cited by 28 publications

References 37 publications

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities

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Regulation of Blood Pressure by Targeting Ca V 1.2-Galectin-1 Protein Interaction

Cited by 28 publications

References 37 publications

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

Tissue factor cytoplasmic domain exacerbates post-infarct left ventricular remodeling via orchestrating cardiac inflammation and angiogenesis

Partners in Crime: Towards New Ways of Targeting Calcium Channels

Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities

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Regulation of Blood Pressure by Targeting Ca _V 1.2-Galectin-1 Protein Interaction