Table 2.

Pivotal studies identifying the role of shear stress and perivascular adipose tissue. The references represent the progression in the text according to those reported in the PRISMA flowchart.

First Author/Year Ref	Type of Study	Cohort	Aims	Findings
Shindo et al. 2016 Arterioscler Thromb Vasc Biol [51]	Mouse model	Mouse Lipus Vs Mouse non Lipus	LIPUS implicated in amelioration of LV remodeling after IMA. Elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS.	LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo. Increased vascular endothelial growth factor signaling
Hatanaka et al. 2016 Am J Physiol Cell Physiol [52]	Human model	HUVECs Vs HUVECs Knockdown of caveolin-1 or β1-integrin	Effects of SW irradiation on intracellular signaling pathways in vitro to induce myocardial angiogenesis	Activation of caveolin-1 and β1-integrin, and subsequent phosphorylation of Erk and Akt play crucial roles in the SW-induced angiogenesis.
Friederich-Persson et al. 2017 Arterioscler Thromb Vasc Biol [53]	Rat model	Wild-type Nox4−/−	Regulatory role and vasoprotective effects of BAT	BAT, via Nox4-derived hydrogen peroxide, induces cyclic GMP-dependent protein kinase G type-1α activation, resulting in reduced vascular contractility
Burgoyne et al. 2007 Science [54]	Mice model	SM22+, Nox5+, Nox5+/SM22+ † WT	Whether concentration of oxydants in cells can regulate biochemical signaling mechanisms	Oxydants lead to cGMP-independent vasorelaxation in the cardiovascular system. H2O2 can operate as an endothelium-derived hyperpolarizing factor
Prysyazhna et al. 2012 Nat Med. 2012 [55]	Mice model	WT KI	Importance of PKGI-α oxidation in the EDHF mechanism and blood pressure control in vivo	C42S ‘redox-dead’ version of PKGI-α blocked the vasodilatory action of H2O2 on resistance vessels resulting in hypertension in vivo.
Noblet et al. 2015 Arterioscler Thromb Vasc Biol [56]	Suine model	Ossabaw swine obese vs. lean	Effects of lean and obese coronary PVAT on coronary vasodilation	Lean and obese coronary PVAT attenuates vasodilation via inhibitory effects on vascular smooth muscle K (+) channels. Calpastatin initiate or lead to progression of smooth muscle dysfunction in obesity.
Dou et al. 2017 Arterioscler Thromb Vasc [57]	Human model	AT-RAA (N = 74) AT-Mediastianal (n = 74)	AT-expressed ADAM17 activation in development of coronary microvascular dysfunction in obesity.	Aging and obesity decrease caveolin-1 expression. Increased vascular endothelial ADAM17 activity and soluble TNF release in AT
Candela et al. 2017 [58] Arterioscler Thromb Vasc	Mice model	Mice obese vs. lean	Role of macrophages in determining vascular [H2S] and vasodilatation	Vascular H2S depletion sustains the loss of perivascular adipose tissue anticontractile function in obesity.
Xia et al. 2016 Arterioscler Thromb Vasc Bio [59]	Mice model	C57BL/6J fat diet with or without PVAT	Contribution of PVAT to vascular dysfunction.	Diet-induced obesity leads to l-arginine deficiency and eNOS uncoupling in PVAT
Bussey et al. 2018 Arterioscler Thromb Vasc Biol [60]	Rat Model	Mesenteric arteries with and without PVAT from control	PVAT function after weight loss induced by caloric restriction	Diet-induced weight loss reverses obesity-induced PVAT damage due to reduced inflammation and increased nitric oxide synthase activity within PVAT

Abbreviations: Akt = protein kinase, AT = adipose tissue, ADAM17 = Tumour necrosis factor-α [TNF]-converting enzyme, BAT = brown adipose tissue, cGMP = guanosine 3′,5′-monophosphate, Cav-1 = caveolin-1, EDHF = Endothelium-derived hyperpolarizing factor, eNOS = endothelial NOS, Erk = extracellular signal-regulated kinase, H₂O₂ = hydrogen peroxide, H₂S = hydrogen sulphide, HDF = high-fat diet, LIPUS = low-intensity pulsed ultrasound, LV = left ventricular, PKGIα = protein kinase G I-α, PVAT = perivascular adipose tissue, OS = reactive oxygen species, RAA = right atrial appendance, TNF = tumour necrosis factor, HUVEC = umbilical vein endothelial cell, WT = wild type.