Fibroblast TGFβ signaling in systolic & diastolic🫀functions
Protective▶️Lean 🐭
Pathogenic▶️Diabetic db/db🐭
Evidence from
Fibroblast Tgfbr2 or Smad3 KO🐭
Speckle-tracking echo
👉Peak systolic/diastolic longitudinal endocardial/epicardial strain
#CardiovascRes 2024
academic.oup.com/cardiovascre...
What are Markers of arterial adventitial fibroblast?
PDGFRA
DPEP1
3 fibroblast subsets
CD55+
LOX+
CXCL14+
CD55+ adventitial fibroblasts are enriched in thoracic aorta & carotid artery, but rare in other large arteries
#CardiovascRes 2023
academic.oup.com/cardiovascre...
PRMT5 di-methylates H3R8 & H4R3▶️
⏬Myocardin-dependent #SmoothMuscleCell contractile gene transcription
⏫SMC proliferation/migration & intimal hyperplasia in injured🐭carotid artery
PRMT5 (& PRMT4) ⬆️in PDGBB-treated SMC &👤coronary #Atherosclerosis
#CardiovascRes 2023
academic.oup.com/cardiovascre...
PRMT5 methylates & stabilizes KLF4 protein▶️
⏫#SmoothMuscleCell proliferation/migration & intimal hyperplasia in injured🐭carotid artery
Evidence from #SmoothMuscleCell PRMT5 KO🐭 & Lentiviral PRMT5
PRMT5⬆️ in👤carotid stenosis & PDGF-BB-treated SMC
#CardioVascRes 2023
academic.oup.com/cardiovascre...
#Atherosclerosis Epitranscriptomics
Mettl3-YTHDF3⏫m6A-MTRFA mRNA in SMCs➡️
⏫cholesterol-induced Mφ-like phenotype
SMC Mettl3 KO🐭+HFD AAV-PCSK9➡️
⏬Lesion burden, necrotic core, Mφ
👉Abolishes SMC contribution to lesion!
👉Reverted by AAV9-SM22-MRTFA
#CardiovascRes 2025
academic.oup.com/cardiovascre...
#SmoothMuscleCell m6A Epitranscriptomics
METTL3 as a direct target gene of YY1
METTL3-IGF2BP1 stabilizes MYH11 MYLK2 TGFβ2 mRNAs
SMC Yy1 or Mettl3 KO🐭
⏬vasoconstriction
↔️vasorelaxation
AAV-SM22-METTL2 iv ⏫arterial contractility of SMC Yy1 KO🐭
#CardiovascRes 2025
academic.oup.com/cardiovascre...
Heart #Lymphangiogenesis
"Endogenous lymphangiogenesis⬇️TAC-induced 🫀 inflammation & perivascular fibrosis, delaying #HeartFailure development in C57BL/6 but not in Balb/c🐭"
anti-VEGFR3 Ab B6🐭
⏫perivasc fibrosis
⏫Mφ NK B
@hfpef-diva.bsky.social #CardiovascRes 2023
academic.oup.com/cardiovascre...
Integrated proteomics identifies troponin I isoform switch as a regulator of a sarcomere-metabolism axis during cardiac regeneration #CardiovascRes #MassSpec academic.oup.com/cardiovascre...
DJ-1/PARK7 (causal gene of #ParkinsonDisease)⏬Diabetic #VascularCalcification
Acetylation (by NAT10)-Ubiquitination (by TRIM32) cascade degrades DJ-1▶️
⏫STAT1 & RAGE
⏫#SmoothMuscleCell Osteogenesis
⏫SMC MFGE8+ #MatrixVesicle▶️
⏫MV-collagen binding
#CardiovascRes 2024
academic.oup.com/cardiovascre...
#AlternativeSplicing #SmoothMuscleCell
RBPMS, coordinating with RBFOX2, mediates splicing events of SMC contractile, focal adhesion & actin cytoskeleton genes
234 skipped exon events shared by high-level RBPMS overexpression in hESC adult aorta
#CardiovascRes 2024
academic.oup.com/cardiovascre...
Pericytes in the brain & heart: functional roles & response to ischaemia & reperfusion
"pericyte-mediated capillary constriction plays a key role in restricting blood flow after ischaemia"
Also in #SkeletalMuscle, Kidney or Diabetic Islets?😆
#CardiovascRes 2024
academic.oup.com/cardiovascre...
#SmoothMuscleCell #Atherosclerosis
SMC CCN2/CTGF KO creates a striking #Glycosaminoglycan-depositing & LDL-entrapping, pro-atherogenic phenotype😎◀️What is the cellular mechanism?🧐
What a crazy Fatty mouse Aorta!🤯
#CardiovascRes 2024
academic.oup.com/cardiovascre...
Inactivation of🐭Ogg1, an essential #BaseExcisionRepair enzyme that repairs 8-oxoguanine ▶️
#ArterialStiffening without altered collagen fibril abundance
A very sophisticated #Matrisome related to #Aging-related #OxidativeDNADamage
#CardiovascRes 2024
academic.oup.com/cardiovascre...
Transcriptomes of #LiverSinusoidalEndothelialCell & #GlomerularEndothelialCell of BMP9 KO🐭
#ArterioVenousMalformation/AV Shunting in liver intestine uterine
Arterial dilation/tortuosity in lung brain
#CardiovascRes 2024
academic.oup.com/cardiovascre...
#AngiotensinConvertingEnzyme as a major regulator of Macrophage Lipid Metabolism
+a potential role of PPARα
ACE 10/10 mice are resistant to #Atherosclerosis, with ⏫M2-like CD206+IL10+ACE+ macrophages
So ACEi can exacerbate #Atherosclerosis???😧
#CardiovascRes 2023
academic.oup.com/cardiovascre...
#Hepatocyte #Mitchondria #Atherosclerosis
Mito-dependent/-independent roles of DRP1 in hepatic PCSK9 expression
Mdivi-1, a DRP1 inhibitor->
⏬SREBP-1c->⏬PCSK9 transcription
Modulating hepatocyte secretome->⏬PCSK9 secretion, ⏫PCSK9 degradation
#CardiovascRes 2021
academic.oup.com/cardiovascre...
#SmoothMuscleCell MMP3 mediates #ArterialCalcification in mice+Vitamin D3 (How?🧐)
MMP3 is the only MMP upregulated in calcifying rat aortic SMCs (Pi/Ca2+)
Raul Guzman lab #CardiovascRes 2024
academic.oup.com/cardiovascre...
αSMA+ #SmoothMuscleCell-TRAP;Ldlr−/−;ApoB100/100🐭▶️SMC Translatome in #Atherosclerosis
Novel atherosclerosis proteins
Spink5
Atp1a4
Gm13293
Hs6st2
Itih4
Smim3
Pcdh11x
No EndMT trait detected
#CardiovascRes 2024
academic.oup.com/cardiovascre...
Transcriptional driver ZBTB11 of #Cardiomyocyte degeneration (#Autophagy #Apoptosis) in PKP2 #ArrhythmogenicCardiomyopathy
Tomo-seq
RNAseq of 214 100-μm cryosections of👤LV wall
Epicardium-to-Endocardium🤠
#SpatialTranscriptomics
#CardiovascRes 2022
academic.oup.com/cardiovascre...
Genetic (p16-3MR) vs Pharmacological (ABT263) #Senolysis in ApoE-/-🐭#Atherosclerosis
p16-3MR: No benefits
ABT263:⏬lesion👉senolyis+leukocyte depletion
Proliferating Mφ are also p16+;SAβGal+
🧐#Senescence in situ?
Martin Bennett lab #CardiovascRes 2022
academic.oup.com/cardiovascre...
