Letter by Jin et al Regarding Article, "SPARC, A Novel Regulator of Vascular Cell Function in Pulmonary Hypertension".

Abstract

HomeCirculationVol. 146, No. 5Letter by Jin et al Regarding Article, “SPARC, A Novel Regulator of Vascular Cell Function in Pulmonary Hypertension” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Jin et al Regarding Article, “SPARC, A Novel Regulator of Vascular Cell Function in Pulmonary Hypertension” Qi Jin, MD, Lihua Guan, MD and Daxin Zhou, MD Qi JinQi Jin https://orcid.org/0000-0003-3307-3663 From Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, China. *Q. Jin and L. Guan contributed equally. Search for more papers by this author , Lihua GuanLihua Guan From Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, China. *Q. Jin and L. Guan contributed equally. Search for more papers by this author and Daxin ZhouDaxin Zhou https://orcid.org/0000-0002-9926-5708 From Department of Cardiology, Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University, China. Search for more papers by this author Originally published1 Aug 2022https://doi.org/10.1161/CIRCULATIONAHA.122.060195Circulation. 2022;146:e14–e15To the Editor:We congratulate Veith et al1 for their meaningful work recently published in Circulation. They comprehensively investigated the potential role of secreted protein acidic and rich in cysteine (SPARC) in the pathogenesis of pulmonary hypertension (PH) by unbiased novel laser-assisted microdissection and transcriptomics-based consecutive screening approach and demonstrated that upregulated SPARC disrupted pulmonary vascular cell function and in vivo SPARC knockdown improved hemodynamic and cardiac function, indicating that quenching the SPARC ignited from the lung to the right heart may have potential implications for reversing PH progression. However, there is still a long way to go for SPARC translation from bench to bedside.SPARC expression was elevated in lung tissues of mice exposed to chronic hypoxia and patients with idiopathic pulmonary arterial hypertension, but paradoxically, circulating SPARC was significantly lower in patients with idiopathic pulmonary arterial hypertension compared with healthy control subjects, which needs to be confirmed by further studies because of the small sample size.1 In addition, patients with idiopathic pulmonary arterial hypertension were not the optimal study population because differential proteins were screened on the basis of the transcriptome of the reoxygenation process. In addition, there were enormous differences in pathophysiology between hypoxia-induced PH and idiopathic pulmonary arterial hypertension; patients with PH attributable to lung diseases or hypoxia may be more appropriate. SPARC and its family protein SPARCL1 (also known as Hevin) have previously been shown to be elevated in the right ventricle of monocrotaline-induced PH,2 and SPARCL1 was associated with right ventricular pathological maladaptation and ventricular arterial uncoupling in PH,3 indicating a potential role of SPARC family proteins in right ventricular homeostasis. Nevertheless. the present study focused mainly on pulmonary vasculature and neglected secondary right-sided heart failure.1 To the best of our knowledge, the exact role of SPARC has never been addressed in pathological right ventricular remodeling. SPARC has recently been reported to regulate E-cadherin protein expression and to be involved in endothelial to mesenchymal transition,4 an essential process implicated in PH development and progression.5 Here, it remains unclear whether SPARC mediates endothelial to mesenchymal transition to trigger PH. Last, SPARC silencing did not protect against PH, as evidenced by the fact that congenital SPARC knockout did not differ from wild-type mice exposed to chronic hypoxia. Pulmonary smooth muscle cells isolated from knockout mice even proliferated more vigorously than control cells under hypoxia, suggesting that excessive intervention of SPARC might aggravate the condition. Thus, appropriately and precisely controlling the degree of intervention is particularly critical.Although there are many issues and uncertainties to be clarified, this study has taken an important and amazing step in revealing PH pathogenesis. More studies are needed to validate these results and to further explore the role of SPARC in different PH subtypes in appropriate populations and animal models.Article InformationSources of FundingThis work was supported in part by the Yangfan Project of Science and Technology Commission of Shanghai Municipality (No. 22YF1439500).Disclosures None.FootnotesCirculation is available at www.ahajournals.org/journal/circ*Q. Jin and L. Guan contributed equally.