Role of biomarkers in evaluation, treatment and clinical studies of pulmonary arterial hypertension

Hemnes, Anna R.; Rothman, Alexander; Swift, Andrew J.; Zisman, Lawrence S.

doi:10.1177/2045894020957234

Cited by 21 publications

(27 citation statements)

References 123 publications

(222 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…stratify clinical severity and mortality risk), (c) act as surrogate end‐points (i.e. monitor treatment effect), or (d) predict response to therapy 47 . While most biomarker studies in PAH have centered on diagnosis, prognosis, and surrogate end‐points, there is a critical unmet need to identify predictors of therapy response.…”

Section: Evaluating Biomarkers Of Disease Activitymentioning

confidence: 99%

What’s new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference

Sweatt¹,

Reddy

Rahaghi

et al. 2021

Pulm. circ.

View full text Add to dashboard Cite

In this conference paper, we review the 2020 American Thoracic Society (ATS) International Conference session titled, âWhatâs New in Pulmonary Hypertension Clinical Research: Lessons from the Best Abstractsâ. This virtual mini-symposium took place on October 21, 2020, in lieu of the annual in-person ATS International Conference which was cancelled due to the COVID-19 pandemic. Seven clinical research abstracts were selected for presentation in the session, which encompassed five major themes: (1) standardizing diagnosis and management of pulmonary hypertension, (2) improving risk assessment in pulmonary arterial hypertension, (3) evaluating biomarkers of disease activity, (4) understanding metabolic dysregulation across the spectrum of pulmonary hypertension, and (5) advancing knowledge in chronic thromboembolic pulmonary hypertension. Focusing on these five thematic contexts we review the current state of knowledge, summarize presented research abstracts, appraise their significance and limitations, and then discuss relevant future directions in pulmonary hypertension clinical research.

show abstract

Section: Evaluating Biomarkers Of Disease Activitymentioning

confidence: 99%

What’s new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference

Sweatt¹,

Reddy

Rahaghi

et al. 2021

Pulm. circ.

View full text Add to dashboard Cite

show abstract

“…Pulmonary arterial hypertension (PAH) is a complex disease resulted from the interplay of several biological and environmental processes leading to pulmonary vasculature remodeling, therefore pulmonary hypertension [ 1 ]. Consequently, the low-pressure, thin-walled, crescent-shaped RV has to overcome structural changes to accomplish its function and pump against such an increased afterload [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Despite the publication of 41 randomized clinical trials in the past 25 years and the regulatory approval of multiple drugs delivered by four administration routes [ 3 ], there is no drug focused on improving RV performance and/or reducing inflammation [ 4 ]. Despite currently available therapies PAH patients remain significant morbidity and mortality [ 1 ]. A polyphenol from the stilbene family, 3,5,4′-trihydroxystilbene resveratrol (RES), has drawn researchers' attention by its cardioprotective activity in other cardiovascular diseases [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension

Bernal‐Ramírez

Silva-Platas

Jerjes‐Sánchez

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vessel remodeling; however, its severity and impact on survival depend on right ventricular (RV) failure. Resveratrol (RES), a polyphenol found in red wine, exhibits cardioprotective effects on RV dysfunction in PAH. However, most literature has focused on RES protective effect on lung vasculature; recent finding indicates that RES has a cardioprotective effect independent of pulmonary arterial pressure on RV dysfunction, although the underlying mechanism in RV has not been determined. Therefore, this study is aimed at evaluating sirtuin-3 (SIRT3) modulation by RES in RV using a monocrotaline- (MC-) induced PAH rat model. Myocyte function was evaluated by confocal microscopy as cell contractility, calcium signaling, and mitochondrial membrane potential ( Δ Ψ m ); cell energetics was assessed by high-resolution respirometry, and western blot and immunoprecipitation evaluated posttranslational modifications. PAH significantly affects mitochondrial function in RV; PAH is prone to mitochondrial permeability transition pore (mPTP) opening, thus decreasing the mitochondrial membrane potential. The compromised cellular energetics affects cardiomyocyte function by decreasing sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) activity and delaying myofilament unbinding, disrupting cell relaxation. RES partially protects mitochondrial integrity by deacetylating cyclophilin-D, a critical component of the mPTP, increasing SIRT3 expression and activity and preventing mPTP opening. The preserved energetic capability rescues cell relaxation by maintaining SERCA activity. Avoiding Ca2+ transient and cell contractility mismatch by preserving mitochondrial function describes, for the first time, impairment in excitation-contraction-energetics coupling in RV failure. These results highlight the importance of mitochondrial energetics and mPTP in PAH.

show abstract

“…Specific treatment includes therapies targeting endothelin, nitric oxide, and prostacyclin pathways in pulmonary arteries to decrease pulmonary pressure and prevent RV stress [ 3 ]. The available therapeutic approaches improve quality of life and reduce the incidence of clinical worsening [ 4 ]. Although RV dysfunction and the patient's response to PAH-specific treatment determine survival [ 5 , 6 ], there are no therapeutic aims to improve RV dysfunction [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction

Bernal‐Ramírez

Díaz-Vesga

Talamilla

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The right and left ventricles have traditionally been studied as individual entities. Furthermore, modifications found in diseased left ventricles are assumed to influence on right ventricle alterations, but the connection is poorly understood. In this review, we describe the differences between ventricles under physiological and pathological conditions. Understanding the mechanisms that differentiate both ventricles would facilitate a more effective use of therapeutics and broaden our knowledge of right ventricle (RV) dysfunction. RV failure is the strongest predictor of mortality in pulmonary arterial hypertension, but at present, there are no definitive therapies directly targeting RV failure. We further explore the current state of drugs and molecules that improve RV failure in experimental therapeutics and clinical trials to treat pulmonary arterial hypertension and provide evidence of their potential benefits in heart failure.

show abstract

Role of biomarkers in evaluation, treatment and clinical studies of pulmonary arterial hypertension

Cited by 21 publications

References 123 publications

What’s new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference

What’s new in pulmonary hypertension clinical research: lessons from the best abstracts at the 2020 American Thoracic Society International Conference

Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension

Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction

Contact Info

Product

Resources

About