Ernesto Oqueli

Sympathetic nerves innervate bone marrow and various immune organs, where norepinephrine—the primary sympathetic neurotransmitter—directly interacts with immune cells that express adrenergic receptors. This article reviewed the key molecular pathways triggered by sympathetic activation and explored how sympathetic activity influences immune cell migration. Norepinephrine serves as a chemoattractant for monocytes, macrophages, and stem cells, promoting the migration of myeloid cells while inhibiting the migration of lymphocytes at physiological concentrations. We also examined the role of immune cell infiltration in cardiovascular diseases and cancer. Evidence suggests that sympathetic activation increases myeloid cell infiltration into target tissues across various cardiovascular diseases, including atherosclerosis, hypertension, cardiac fibrosis, cardiac hypertrophy, arrhythmia, myocardial infarction, heart failure, and stroke. Conversely, inhibiting sympathetic activity may serve as a potential therapeutic strategy to treat these conditions by reducing macrophage infiltration. Furthermore, sympathetic activation promotes macrophage accumulation in cancer tissues, mirroring its effects in cardiovascular diseases, while suppressing T lymphocyte infiltration into cancerous sites. These changes contribute to increased cancer growth and metastasis. Thus, inhibiting sympathetic activation could help to protect against cancer by enhancing T cell infiltration and reducing macrophage presence in tumors.

Sympathetic nerves innervate bone marrow and various immune organs, where norepinephrine—the primary sympathetic neurotransmitter—directly interacts with immune cells that express adrenergic receptors. This article reviewed the key molecular pathways triggered by sympathetic activation and explored how sympathetic activity influences immune cell migration. Norepinephrine serves as a chemoattractant for monocytes, macrophages, and stem cells, promoting the migration of myeloid cells while inhibiting the migration of lymphocytes at physiological concentrations. We also examined the role of immune cell infiltration in cardiovascular diseases and cancer. Evidence suggests that sympathetic activation increases myeloid cell infiltration into target tissues across various cardiovascular diseases, including atherosclerosis, hypertension, cardiac fibrosis, cardiac hypertrophy, arrhythmia, myocardial infarction, heart failure, and stroke. In contrast, inhibiting sympathetic activity may serve as a potential therapeutic strategy to treat these conditions by reducing macrophage infiltration. Furthermore, sympathetic activation suppresses T lymphocyte infiltration and promotes macrophage accumulation in cancer tissues, which are linked to increased cancer growth and metastasis. Thus, inhibiting sympathetic activation could help protect against cancer by enhancing T cell infiltration and reducing macrophage presence in tumors.

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005–2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006–2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment–elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.

The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100 μM) inhibited the increase in inflammatory gene expression and apoptosis induced by acrolein and hydrogen peroxide, two oxidants that may play a role in AAA pathogenesis. The anti-apoptotic effect of hydralazine was associated with a decrease in caspase 8 gene expression. In a mouse model of AAA induced by subcutaneous angiotensin II infusion (1 µg/kg body weight/min) for 28 days in apolipoprotein E-deficient mice, hydralazine treatment (24 mg/kg/day) significantly decreased AAA incidence from 80% to 20% and suprarenal aortic diameter by 32% from 2.26 mm to 1.53 mm. Hydralazine treatment also significantly increased the survival rate from 60% to 100%. In conclusion, hydralazine inhibited AAA formation and rupture in a mouse model, which was associated with its anti-inflammatory and anti-apoptotic properties.

Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, β1, β2, and β3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of β blockers and β3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established.

Purpose During the COVID-19 pandemic, widespread public health measures were implemented to control community transmission. The association between these measures and health-related quality of life (HRQOL) among patients following percutaneous coronary intervention has not been studied. Methods We included consecutive patients undergoing percutaneous coronary intervention (PCI) in the state-wide Victorian Cardiac Outcomes Registry between 1/3/2020 and 30/9/2020 (COVID-19 period; n = 5024), with a historical control group from the identical period one year prior (control period; n = 5041). HRQOL assessment was performed via telephone follow-up 30 days following PCI using the 3-level EQ-5D questionnaire and Australian-specific index values. Results Baseline characteristics were similar between groups, but during the COVID-19 period indication for PCI was more common for acute coronary syndromes. No patients undergoing PCI were infected with COVID-19 at the time of their procedure. EQ-5D visual analogue score (VAS), index score, and individual components were higher at 30 days following PCI during the COVID-19 period (all P < 0.01). In multivariable analysis, the COVID-19 period was independently associated with higher VAS and index scores. No differences were observed between regions or stage of restrictions in categorical analysis. Similarly, in subgroup analysis, no significant interactions were observed. Conclusion Measures of HRQOL following PCI were higher during the COVID-19 pandemic compared to the previous year. These data suggest that challenging community circumstances may not always be associated with poor patient quality of life.