HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension.

Background: Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic phenotype. However, the function of HMGB2 in PH remains uninvestigated.

Elevated serum levels of leukocyte cell-derived chemotaxin 2 are associated with the prevalence of metabolic syndrome.

Aims: Inflammation is central to the pathogenesis of metabolic syndrome (MetS). Leukocyte cell-derived chemotaxin 2 (LECT2) is constitutively secreted in response to inflammatory stimuli and oxidative stress contributing to tissue or systemic inflammation. We explored the relationship between LECT2 levels and MetS severity in humans and mice.

Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH), Group 1 pulmonary hypertension (PH), is a type of pulmonary vascular disease characterized by abnormal contraction and remodeling of the pulmonary arterioles, manifested by pulmonary vascular resistance (PVR) and increased pulmonary arterial pressure, eventually leading to right heart failure or even death. The mechanisms involved in this process include inflammation, vascular matrix remodeling, endothelial cell apoptosis and proliferation, vasoconstriction, vascular smooth muscle cell proliferation and hypertrophy. In this study, we review the mechanisms of action of prostaglandins and their receptors in PAH.

HMGB family proteins: Potential biomarkers and mechanistic factors in cardiovascular diseases.

Cardiovascular disease (CVD) is the most fatal disease that causes sudden death, and inflammation contributes substantially to its occurrence and progression. The prevalence of CVD increases as the population ages, and the pathophysiology is complex. Anti-inflammatory and immunological modulation are the potential methods for CVD prevention and treatment.

Inflachromene inhibits intimal hyperplasia through the HMGB1/2- regulated TLR4-NF-κB pathway.

The contractile-syntheticphenotypicconversion of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis, vascular restenosis, and hypertension. Our previous study explored the correlation between high mobility group box protein (HMGB) 1 and HMGB2 and neointimal hyperplasia after vascular injury. In the present study, we explore whether inflachromene (ICM), a novel inhibitor of the expression of both HMGB1 and HMGB2, modulates phenotypic changes in VSMCs and the mechanisms involved.

Legumain is a predictor of all-cause mortality and potential therapeutic target in acute myocardial infarction.

The prognostic impact of extracellular matrix (ECM) modulation and its regulatory mechanism post-acute myocardial infarction (AMI), require further clarification. Herein, we explore the predictive role of legumain-which showed the ability in ECM degradation-in an AMI patient cohort and investigate the underlying mechanisms. A total of 212 AMI patients and 323 healthy controls were enrolled in the study.

Niacin Attenuates Pulmonary Hypertension Through H-PGDS in Macrophages.

Rationale: Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling, accompanied by varying degrees of perivascular inflammation. Niacin, a commonly used lipid-lowering drug, possesses vasodilating and proresolution effects by promoting the release of prostaglandin D (PGD). However, whether or not niacin confers protection against PAH pathogenesis is still unknown.

Association between Cardiovascular Burden and Requirement of Intensive Care among Patients with Mild COVID-19.

Background: Information regarding the impact of cardiovascular (CV) conditions on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited.

Methods: This study evaluated the association of underlying CV conditions with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to the designated hospital for intensive care due to COVID-19 disease progression.

Osteoprotegerin promotes intimal hyperplasia and contributes to in-stent restenosis: Role of an αVβ3/FAK dependent YAP pathway.

Objective: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are related to in-stent-restenosis (ISR) following percutaneous coronary intervention (PCI). Osteoprotegerin (OPG) has been implicated in various vascular diseases. However, the effects of OPG on ISR and the underlying mechanism remained elusive.

Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling.

Vascular remodeling, including smooth muscle cell hypertrophy and proliferation, is the key pathological feature of pulmonary arterial hypertension (PAH). Prostaglandin I analogs (beraprost, iloprost, and treprostinil) are effective in the treatment of PAH. Of note, the clinically favorable effects of treprostinil in severe PAH may be attributable to concomitant activation of DP1 (D prostanoid receptor subtype 1).

Successful COMPASS, Disappointing COMMANDER HF, What Have We Learned From These Two Trials?

Despite considerable progress in the field of heart failure about drugs and device therapy, the mortality rate of patients with heart failure remains high. Studies have shown that thromboembolism and stroke are associated with high mortality in patients with heart failure. Although warfarin therapy reduces the rate of ischemic stroke in patients with heart failure, the overall benefit from warfarin in this population seems to be offset by the increased bleeding risk.

Blood Collection Through Subclavian Vein Puncture in Mice.

The mouse is the foremost mammalian model for studying human disease and human health. However, blood sample collection from mice is challenging in research work. Tail blood collection is a popular method when a small amount of blood sample is needed.

Macrophage-Derived Legumain Promotes Pulmonary Hypertension by Activating the MMP (Matrix Metalloproteinase)-2/TGF (Transforming Growth Factor)-β1 Signaling.

Objective- Macrophages participate in the pathogenesis of pulmonary arterial hypertension (PAH). Lgmn (Legumain), a newly discovered cysteine proteinase belonging to the C13 peptidase family, is primarily expressed in macrophages; however, its roles in PAH remain unknown. Approach and Results- Herein, Lgmn was upregulated in lung tissues of PAH mice subjected to hypoxia plus SU5416 and PAH rats challenged with monocrotaline.

RAGE-mediated extracellular matrix proteins accumulation exacerbates HySu-induced pulmonary hypertension.

Aims: Extracellular matrix (ECM) proteins accumulation contributes to the progression of pulmonary arterial hypertension (PAH), a rare and fatal cardiovascular condition defined by high pulmonary arterial pressure, whether primary, idiopathic, or secondary to other causes. The receptor for advanced glycation end products (RAGE) is constitutively expressed in the lungs and plays an important role in ECM deposition. Nonetheless, the mechanisms by which RAGE mediates ECM deposition/formation in pulmonary arteries and its roles in PAH progression remain unclear.

Osteoprotegerin Disruption Attenuates HySu-Induced Pulmonary Hypertension Through Integrin αvβ3/FAK/AKT Pathway Suppression.

Background: Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). Clinical studies have suggested a correlation between osteoprotegerin serum levels and PAH severity. Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity.

Serum levels of tumor necrosis factor-related apoptosis-inducing ligand correlate with the severity of pulmonary hypertension.

Pulmonary hypertension (PH) is a rapidly progressive disease that eventually leads to right heart failure and death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-Rs) play an important role in the survival, migration, and proliferation of vascular smooth muscle cells. However, the association between serum TRAIL levels and PH is unknown.

EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling.

Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia.

Vitamin D inhibits COX-2 expression and inflammatory response by targeting thioesterase superfamily member 4.

Inadequate vitamin D status has been linked to increased risk of type 2 diabetes and cardiovascular disease. Inducible cyclooxygenase (COX) isoform COX-2 has been involved in the pathogenesis of such chronic inflammatory diseases. We found that the active form of vitamin D, 1,25(OH)2D produces dose-dependent inhibition of COX-2 expression in murine macrophages under both basal and LPS-stimulated conditions and suppresses proinflammatory mediators induced by LPS.