LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats

Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia

“…Another important source of ROS in pathological processes is the nicotinamide adenine dinucleotide oxidase (NADPH oxidase) complex, which contains catalytic isoforms called Nox (1-5) and Doux1/2 that form a heterodimer with a lower-molecular-weight subunit called p22phox; this heterodimeric cytochrome is the site of electron transfer to produce O 2 • − or H 2 O 2 depending on the subunit [33]. Among the Nox isoforms, both Nox2 and Nox4 are the principal isoforms in the heart [33], and their expression are related to the hypertrophy process and HF [20,33,48]. This is supported by studies that show that hypertension-induced hemodynamic stress produces activation of NADPH oxidases, and these products (ROS) can lead to inflammation through NF-kB and activator protein 1 (AP-1) activation, stimulating monocyte chemoattractant protein-1 (MCP-1), also known as CCL2, producing monocyte and macrophage infiltration [49,50].…”

“…Despite the large amount of information that explains RVH by PH-induced PO, we cannot ignore that hypoxia triggers the activation of several molecular pathways that could contribute to both the hypertrophic effect and the dilation process in RV. In fact, studies under hypoxic conditions have determined the important role of oxidative stress [20,21], kinase activation [22,23] and inflammatory processes [24] as possible contributors to RVH development and to the transition to right heart failure (RHF) [25].…”

Targeting LOX‐1 in atherosclerosis and vasculopathy: current knowledge and future perspectives

“…Hypoxia also enhances lipid uptake by LOX‐1 in macrophages . Recently, the function of LOX‐1 in a hypoxia rat model was examined . Under normal conditions, LOX‐1 expression is low, but after hypoxia exposure, LOX‐1 expression is increased not only in macrophages, but also in cardiac cells and pulmonary arteries .…”

“…Recently, the function of LOX‐1 in a hypoxia rat model was examined . Under normal conditions, LOX‐1 expression is low, but after hypoxia exposure, LOX‐1 expression is increased not only in macrophages, but also in cardiac cells and pulmonary arteries . Hypoxic conditions also induce the proliferation of VSMCs in the pulmonary artery by activating LOX‐1 .…”

“…Under normal conditions, LOX‐1 expression is low, but after hypoxia exposure, LOX‐1 expression is increased not only in macrophages, but also in cardiac cells and pulmonary arteries . Hypoxic conditions also induce the proliferation of VSMCs in the pulmonary artery by activating LOX‐1 . However, LOX‐1 inhibition using either siRNA‐mediated knockdown or an LOX‐1 neutralizing http://antibody attenuates hypoxia‐induced VSMC proliferation and mediates a contractile‐to‐synthetic phenotypic switch via the ERK/Elk‐1/MRTF A/ SRF pathway …”