\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Upregulation of Mechanosensitive Channel Piezo1 Involved in High Shear
Stress-induced Pulmonary Hypertension}



\author[1]{Jiyuan Chen}%
\author[1]{Jinrui Miao}%
\author[2]{Jing Liao}%
\author[3]{Dansha Zhou}%
\author[1]{Ziyi  Wang}%
\author[4]{Ziying Lin}%
\author[5]{Yuqin Chen}%
\author[4]{Chenting Zhang}%
\author[6]{Xiaoyun Luo}%
\author[6]{Yi Li}%
\author[4]{Yue Xing}%
\author[7]{Manjia  Zhao}%
\author[7]{Sophia  Parmisano}%
\author[1]{Haiyang  Tang}%
\author[8]{Jason X.-J. Yuan}%
\author[5]{Kai Yang}%
\author[9]{Dejun Sun}%
\author[7]{Jian Wang}%
\affil[1]{State Key Laboratory of Respiratory Disease}%
\affil[2]{State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University}%
\affil[3]{First Affiliated Hospital of Guangzhou Medical University}%
\affil[4]{First Affiliated Hospital of Guangzhou Medical College}%
\affil[5]{Guangzhou Medical University}%
\affil[6]{State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University}%
\affil[7]{University of California San Diego}%
\affil[8]{ Medicine Section of Physiology Division of Pulmonary, Critical Care and Sleep Medicine Department of Medicine}%
\affil[9]{The People’s Hospital of Inner Mongolia}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: Piezo1 is a crucial mechanical sensitive channel
involved in vascular remodeling. However, the role of Piezo1 in
different types of vascular cells during the development of pulmonary
hypertension (PH) induced by high flow is largely unknown. Experimental
Approach: Based on previously established protocols, we established a
rat PH model by left pulmonary artery ligation (LPAL) for 2 and 5 weeks
to mimic the high flow and hemodynamic stress. Key Results: Results
showed that right ventricular systolic pressure (RVSP) and right
ventricular wall thickness were significantly increased in the LPAL
groups compared with the SHAM group. Rats in LPAL-5w groups developed
remarkable pulmonary vascular remodeling, resulting in decreased
phenylephrine-induced contraction and acetylcholine-induced relaxation.
On the one hand, in pulmonary arterial smooth muscle cells (PASMCs),
upregulation of Piezo1 was observed in association with the elevation of
{[}Ca2+{]}cyt in the PASMCs from both LPAL-2w and LPAL-5w groups versus
respective SHAM groups. Notably, Piezo1 expression was directly
upregulated by YAP/TEAD4. On the other hand, significantly upregulated
Piezo1 expression was also presented in the lung tissues, mostly
composed of pulmonary endothelial cells (ECs), from rats of LPAL-2w and
-5ws groups, which can be transcriptionally regulated by RELA (p65) and
contributes to the lung inflammation. Conclusion and Implications: Our
results suggested the upregulation of Piezo1 in both PASMCs and ECs,
coordinate together and contribute to the pulmonary vascular remodeling
and dysfunction in LPAL-PH rats, providing novel insights into the cell
type-specific effects of Piezo1 in the pulmonary vasculature during high
flow-related PH.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`manuscript-LPAL paper.doc`  available at \url{https://authorea.com/users/458545/articles/555079-upregulation-of-mechanosensitive-channel-piezo1-involved-in-high-shear-stress-induced-pulmonary-hypertension}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-6/Figure-6}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

