A Shocking Deficiency

Penn, Erin H.; Olenchock, Benjamin A.; Marston, Nicholas

doi:10.1161/circulationaha.119.040894

Cited by 12 publications

(11 citation statements)

References 5 publications

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“…Endoglins hydroxylate HIF-1a to promote its degradation; in turn, impaired HIF-1a degradation is associated with increased HIF-1a-dependent pulmonary vasoconstriction and adverse vascular remodeling in PAH. This may explain converging lines of evidence linking scurvy with incident (albeit reversible) PAH (36).…”

Section: Recognizing the Systemic Sequelae Of Pahmentioning

confidence: 84%

Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances

Maron

Abman

Elliott

et al. 2021

Am J Respir Crit Care Med

109

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The diagnosis and management of pulmonary arterial hypertension (PAH) includes several advances, such as a broader recognition of extrapulmonary vascular organ system involvement, validated point-of-care clinical assessment tools, and focus on the early initiation of multiple pharmacotherapeutics in appropriate patients. Indeed, a principal goal in PAH today is an early diagnosis for prompt initiation of treatment to achieve a minimal symptom burden; optimize the patient's biochemical, hemodynamic, and functional profile; and limit adverse events. To accomplish this end, clinicians must be familiar with novel risk factors and the revised hemodynamic definition for PAH. Fresh insights into the role of developmental biology (i.e., perinatal health) may also be useful for predicting incident PAH in early adulthood. Emergent or underused approaches to PAH management include a novel TGF-b ligand trap pharmacotherapy, remote pulmonary arterial pressure monitoring, next-generation imaging using inert gas-based magnetic resonance and other technologies, right atrial pacing, and pulmonary arterial denervation. These and other PAH state of the art advances are summarized here for the wider pulmonary medicine community.

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Section: Recognizing the Systemic Sequelae Of Pahmentioning

confidence: 84%

Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances

Maron

Abman

Elliott

et al. 2021

Am J Respir Crit Care Med

109

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“… 34 Indeed, emerging research on nutritional, pollution, and other acquired contributors to PAH are steering the field toward better models for predicting incident PAH. 35,36 Only in this way can knowledge on the convergence of genetic, molecular, and environmental factors be utilized to individualize pathobiology-phenotype in patients. This progress is within the larger mission in the field toward a precision medicine approach for drug development and clinical trial design.…”

Section: Resultsmentioning

confidence: 99%

Pulmonary arterial hypertension: Cellular and molecular changes in the lung

Maron

2020

gcsp

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The range of cell types identified in the pathogenesis of pulmonary arterial hypertension (PAH) has expanded substantially since the first pathological descriptions of this disease. This, inturn, has provided needed clarity on the gamut of molecular mechanisms that regulate vascular remodeling and promote characteristic cardiopulmonary hemodynamic changes that define PAH clinically. Insight derived from these scientific advances suggest that the PAH arteriopathy is due to the convergence of numerous molecular mechanisms driving cornerstone endophenotypes, such as plexigenic, hypertrophic, and fibrotic histopathological changes. Interestingly, whilesome endophenotypes are observed commonly in multiple cell types, such as dysregulated metabolism, other events such as endothelial-mesenchymal transition are cell type-specific. Integrating data from classical PAH vascular cell types with fresh information in pericytes, adventitial fibroblasts, and other PAH contributors recognized more recently has enriched the field with deeper understanding on the molecular basis of this disease. This added complexity, however, also serves as the basis for utilizing novel analytical strategies that emphasize functional signaling pathways when extracting information from big datasets. With these concepts as the backdrop, the current work offers a concise summary of cellular and molecular changes in the lung that drive PAH and may, thus, be important for discovering novel therapeutic targets or applications to clarify PAH onset and disease trajectory.

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“…Hydroxylated HIFa is then targeted by von Hippel–Lindau protein for ubiquitination and proteasomal degradation. When vitamin C is low, there are increased levels of HIFa which binds with transcription factor HIFb to upregulate transcription of vasoconstrictive genes such as vasoconstrictor endothelin (EDN1) that increase pulmonary vasoconstriction and smooth muscle proliferation [ 4 , 6 ]. This mechanism is similar to vitamin C's role as a cofactor for prolyl and lysyl hydroxylases for collagen synthesis, where a lack of it is attributable to many of scurvy's common manifestations such as poor wound healing, gingival bleeding, and arthralgia [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…In developed countries, smoking history, long-term alcoholism, low income, obesity, psychiatric illness, old age, and voluntarily restrictive diets are risk factors for scurvy [ 1 , 10 ]. In particular, smokers have increased risk of attaining pulmonary hypertension secondary to scurvy as they have three times less vitamin C than nonsmokers and have higher incidences of hypoxia which also increase the levels of HIF [ 4 , 11 ]. Our patient had a long-term history of smoking, psychiatric illness, poor diet, and poor oral intake which all contributed to her vitamin C deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are not any current guidelines or long-term follow-ups (maximum 1 year) to treatments documented. It is thought that vitamin C deficiency leads to pulmonary hypertension secondary to decreased degradation of hypoxia-inducible factor (HIF) and decreased activity of nitrous oxide synthase (NOS) [ 4 , 5 ]. Our case is about a 35-year-old female who was found to have severe pulmonary hypertension in the setting of scurvy.…”

Section: Introductionmentioning

confidence: 99%

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Severe Pulmonary Hypertension in a Patient with Scurvy: Can a Vitamin Reverse It?

Shah

Greene

et al. 2021

Case Reports in Medicine

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Introduction. Pulmonary hypertension secondary to scurvy is a rare manifestation that historically has not been well studied and is only described in a handful of case reports. Case. Our case is about a 35-year-old female with a history significant for drug and tobacco abuse, obesity, poor diet, anxiety, and major depressive disorder who was found to have severe pulmonary hypertension in the setting of vitamin C deficiency (<0.01 mg/L). Conclusion. We present a case that shows pulmonary hypertension can be associated with scurvy and reversed rapidly with adequate vitamin C supplementation.

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A Shocking Deficiency

Cited by 12 publications

References 5 publications

Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances

Pulmonary Arterial Hypertension: Diagnosis, Treatment, and Novel Advances

Pulmonary arterial hypertension: Cellular and molecular changes in the lung

Severe Pulmonary Hypertension in a Patient with Scurvy: Can a Vitamin Reverse It?

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