Regional Variation in Methamphetamine-associated Pulmonary Arterial Hypertension: Who’d Better Call Saul?

Prohaska, Clare C.; Machado, Roberto F.

doi:10.1513/annalsats.202011-1415ed

Cited by 4 publications

(3 citation statements)

References 16 publications

(14 reference statements)

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“…An exemplary gap in this literature involves critical illness due to methamphetamine-associated pulmonary hypertension (Meth-APAH) and right heart failure. Two recently published cohort studies, enrolling patients in pulmonary hypertension specialty clinics, allude to the significance of this problem, particularly in the western United States [20,21]. However, no studies on this topic have been conducted in ICU/hospitalized patients.…”

Section: Critical Illness In Patients With Substance Use Disordersmentioning

confidence: 99%

“…toxic leukoencephalopathy [79] Infections Bacteremia [80]; COVID-19 [81]; dental disease [82]; Two recently published cohort studies, enrolling patients in pulmonary hypertension specialty clinics, allude to the significance of this problem, particularly in the western United States [20,21]. However, no studies on this topic have been conducted in ICU/hospitalized patients.…”

Section: Key Pointsmentioning

confidence: 99%

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Critical care for patients with substance use disorders

Steel,

Bhatraju,

Hills-Dunlap

2023

Current Opinion in Critical Care

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Purpose of review To examine the impact of substance use disorders (SUDs) on critical illness and the role of critical care providers in treating SUDs. We discuss emerging evidence supporting hospital-based addiction treatment and highlight the clinical and research innovations needed to elevate the standards of care for patients with SUDs in the intensive care unit (ICU) amidst staggering individual and public health consequences. Recent findings Despite the rapid increase of SUDs in recent years, with growing implications for critical care, dedicated studies focused on ICU patients with SUDs remain scant. Available data demonstrate SUDs are major risk factors for the development and severity of critical illness and are associated with poor outcomes. ICU patients with SUDs experience mutually reinforcing effects of substance withdrawal and pain, which amplify risks and consequences of delirium, and complicate management of comorbid conditions. Hospital-based addiction treatment can dramatically improve the health outcomes of hospitalized patients with SUDs and should begin in the ICU. Summary SUDs have a significant impact on critical illness and post-ICU outcomes. High-quality cohort and treatment studies designed specifically for ICU patients with SUDs are needed to define best practices and improve health outcomes in this vulnerable population.

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Section: Critical Illness In Patients With Substance Use Disordersmentioning

confidence: 99%

Section: Key Pointsmentioning

confidence: 99%

Critical care for patients with substance use disorders

Steel,

Bhatraju,

Hills-Dunlap

2023

Current Opinion in Critical Care

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“…Its main pathological features include the vasospasm of pulmonary arterioles, hyperplasia of pulmonary intima, and vascular remodeling (Spiekerkoetter et al 2019 ). Recently, more and more data have shown that the frequency and risk of PH are significantly increased in chronic methamphetamine (METH) abusers (Orcholski et al 2017 ; Kolaitis et al 2021 ; Kolaitis and Saggar 2022 ; Prohaska and Machado 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Nupr1-mediated vascular smooth muscle cell phenotype transformation involved in methamphetamine induces pulmonary hypertension

Zhou,

Guo,

et al. 2024

Cell Biol Toxicol

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Aims Nuclear protein 1 (Nupr1) is a multifunctional stress-induced protein involved in the regulation of tumorigenesis, apoptosis, and autophagy. However, its role in pulmonary hypertension (PH) after METH exposure remains unexplored. In this study, we aimed to investigate whether METH can induce PH and describe the role and mechanism of Nupr1 in the development of PH. Methods and results Mice were made to induce pulmonary hypertension (PH) upon chronic intermittent treatment with METH. Their right ventricular systolic pressure (RVSP) was measured to assess pulmonary artery pressure. Pulmonary artery morphometry was determined by H&E staining and Masson staining. Nupr1 expression and function were detected in human lungs, mice lungs exposed to METH, and cultured pulmonary arterial smooth muscle cells (PASMCs) with METH treatment. Our results showed that chronic intermittent METH treatment successfully induced PH in mice. Nupr1 expression was increased in the cultured PASMCs, pulmonary arterial media from METH-exposed mice, and METH-ingested human specimens compared with control. Elevated Nupr1 expression promoted PASMC phenotype change from contractile to synthetic, which triggered pulmonary artery remodeling and resulted in PH formation. Mechanistically, Nupr1 mediated the opening of store-operated calcium entry (SOCE) by activating the expression of STIM1, thereby promoting Ca2+ influx and inducing phenotypic conversion of PASMCs. Conclusions Nupr1 activation could promote Ca2+ influx through STIM1-mediated SOCE opening, which promoted METH-induced pulmonary artery remodeling and led to PH formation. These results suggested that Nupr1 played an important role in METH-induced PH and might be a potential target for METH-related PH therapy. Graphical Abstract 1. Chronic intermittent methamphetamine exposure can induce the development of pulmonary arterial hypertension. 2. Nupr1 plays a key role in the development of methamphetamine-related pulmonary arterial hypertension. 3. Nupr1 mediates PASMCs phenotypic transformation via STIM1signal axis, which results in the development of methamphetamine-related pulmonary arterial hypertension.

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