G protein coupled receptors (GPCRs) are one of the major classes of cell surface receptors and are associated with a group of G proteins consisting of three subunits termed alpha, beta, and gamma. G proteins are classified into four families according to their α subunit; Gα_i, Gα_s, Gα_12/13, and Gα_q. There are several downstream pathways of Gα_q of which the best known is upon activation via guanosine triphosphate (GTP), Gα_q activates phospholipase Cβ, hydrolyzing phosphatidylinositol 4,5-biphosphate into diacylglycerol and inositol triphosphate and activating protein kinase C and increasing calcium efflux from the endoplasmic reticulum. Although G proteins, in particular, the Gα_q/11 are central elements in GPCR signaling, their actual roles have not yet been thoroughly investigated. The lack of research of the role on Gα_q/11 in cell biology is partially due to the obscure nature of the available pharmacological agents. YM-254890 is the most useful Gα_q-selective inhibitor with antiplatelet, antithrombotic, and thrombolytic effects. YM-254890 inhibits Gα_q signaling pathways by preventing the exchange of guanosine diphosphate for GTP. UBO-QIC is a structurally similar compound to YM-254890, which can inhibit platelet aggregation and cause vasorelaxation in rats. Many agents are available for the study of signaling downstream of Gα_q/11. The role of G proteins could potentially represent a novel therapeutic target. This review will explore the range of pharmacological and molecular tools available for the study of the role of Gα_q/11 in GPCR signaling.

Transforming growth factor-β (TGF-β) signaling is initiated by activation of transmembrane TGF-β receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-β signaling pathways leads to pathological conditions. TGF-β signaling is regulated at different levels along the pathways and begins with the liberation of TGF-β ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-β isoforms, enabling precise control of TGF-β signals. In addition, the cell surface compartments used to release active TGF-β are surprisingly vibrant, using thrombospondins, integrins, matrix metalloproteinases and reactive oxygen species. The scope of TGFBR activation is further unfolded with the discovery of TGFBR activation initiated by other signaling pathways. The unique combination of mechanisms works in series to trigger TGFBR activation, which can be explored as therapeutic targets. This comprehensive review provides valuable insights into the diverse mechanisms underpinning TGFBR activation, shedding light on potential avenues for therapeutic exploration.

The endothelium is the single-cell monolayer that lines the entire vasculature. The endothelium has a barrier function to separate blood from organs and tissues but also has an increasingly appreciated role in anti-coagulation, vascular senescence, endocrine secretion, suppression of inflammation and beyond. In modern times, endothelial cells have been identified as the source of major endocrine and vaso-regulatory factors principally the dissolved lipophilic vosodilating gas, nitric oxide and the potent vascular constricting G protein receptor agonists, the peptide endothelin. The role of the endothelium can be conveniently conceptualized. Continued investigations of the mechanism of endothelial dysfunction will lead to novel therapies for cardiovascular disease. In this review, we discuss the impact of endothelial dysfunction on cardiovascular disease and assess the clinical relevance of endothelial dysfunction.